168 results on '"Francesco Cavazzini"'
Search Results
2. P686: REAL-WORLD EFFICACY PROFILE OF ASCIMINIB IN AN ITALIAN, MULTI-RESISTANT CHRONIC-PHASE CHRONIC MYELOID LEUKEMIA (CP-CML) PATIENT POPULATION
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Massimo Breccia, Antonella Russo Rossi, Valentina Giai, Bruno Martino, Carmen Fava, Mario Annunziata, Elisabetta Abruzzese, Gianni Binotto, Claudia Baratè, Aurelio Pio Nardozza, Alessandra Misto, Paola Coco, Valeria Calafiore, Maria Cristina Carraro, Federica Cattina, Francesco Cavazzini, Maria Teresa Corsetti, Lara Crucitti, Monica Crugnola, Paolo Ditonno, Ambra DI Veroli, Anna Ermacora, Felicetto Ferrara, Angelo Genua, Antonella Gozzini, Stefana Impera, Alessandra Iurlo, Luciano Levato, Luigiana Luciano, Maria Cristina Miggiano, Marco De Gobbi, Marco Santoro, Barbara Scappini, Anna Rita Scortechini, Andrea Patriarca, Serena Rosati, Sabina Russo, Rosaria Sancetta, Grazia Sanpaolo, Teresa Maria Santeramo, Silvia Sibilla, Federica Sorà, Paolo Sportoletti, Fabio Stagno, Elena Trabacchi, and Fausto Castagnetti
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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3. P1028: MYELOFIBROSIS (MF) TREATED WITH RUXOLITINIB (RUX) MONOTHERAPY: PREDICTORS OF EARLY DISCONTINUATION AND DEATH ON TREATMENT. THE SHORT-TERM RUX PROGNOSTIC MODEL (STR-PM)
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Francesca Palandri, Giuseppe Auteri, Alessandra Iurlo, Elena Maria Elli, Simona Paglia, Massimiliano Bonifacio, Mario Tiribelli, Malgorzata Monica Trawinska, Nicola Polverelli, Giulia Benevolo, Alessia Tieghi, Florian Heidel, Fabrizio Cavalca, Giovanni Caocci, Eloise Beggiato, Gianni Binotto, Francesco Cavazzini, Maurizio Miglino, Costanza Bosi, Monica Crugnola, Monica Bocchia, Bruno Martino, Novella Pugliese, Marta Venturi, Camilla Mazzoni, Alessandro Isidori, Daniele Cattaneo, Mauro Krampera, Fabrizio Pane, Daniela Cilloni, Gianpietro Semenzato, Roberto M. Lemoni, Antonio Cuneo, Elisabetta Abruzzese, Nicola Vianelli, Michele Cavo, Giuseppe Palumbo, and Massimo Breccia
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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4. A Prognostic Model to Predict Ruxolitinib Discontinuation and Death in Patients with Myelofibrosis
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Francesca Palandri, Giuseppe A. Palumbo, Massimiliano Bonifacio, Elena M. Elli, Mario Tiribelli, Giuseppe Auteri, Malgorzata M. Trawinska, Nicola Polverelli, Giulia Benevolo, Alessia Tieghi, Fabrizio Cavalca, Giovanni Caocci, Eloise Beggiato, Gianni Binotto, Francesco Cavazzini, Maurizio Miglino, Costanza Bosi, Monica Crugnola, Monica Bocchia, Bruno Martino, Novella Pugliese, Marta Venturi, Alessandro Isidori, Daniele Cattaneo, Mauro Krampera, Fabrizio Pane, Daniela Cilloni, Gianpietro Semenzato, Roberto M. Lemoli, Antonio Cuneo, Elisabetta Abruzzese, Filippo Branzanti, Nicola Vianelli, Michele Cavo, Florian Heidel, Alessandra Iurlo, and Massimo Breccia
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ruxolitinib ,myelofibrosis ,prognostic model ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Most patients with myelofibrosis (MF) discontinue ruxolitinib (JAK1/JAK2 inhibitor) in the first 5 years of therapy due to therapy failure. As the therapeutic possibilities of MF are expanding, it is critical to identify patients predisposed to early ruxolitinib monotherapy failure and worse outcomes. We investigated predictors of early ruxolitinib discontinuation and death on therapy in 889 patients included in the “RUX-MF” retrospective study. Overall, 172 patients were alive on ruxolitinib after ≥5 years (long-term ruxolitinib, LTR), 115 patients were alive but off ruxolitinib after ≥5 yrs (short-term RUX, STR), and 123 patients died while on ruxolitinib after p = 0.08). Overall survival (OS) was significantly longer in LTR pts (p = 0.002). In multivariate analysis, PLT < 100 × 109/L, Hb < 10 g/dL, primary MF, absence of spleen response at 3 months and ruxolitinib starting dose
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- 2023
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5. First-Line Treatment of Older Patients with CLL: A New Approach in the Chemo-Free Era
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Antonio Urso, Francesco Cavazzini, Maria Pia Ballardini, Silvia Gambara, Sara Consolo, Gian Matteo Rigolin, and Antonio Cuneo
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chronic lymphocytic leukemia ,older patient ,Bruton tyrosine kinase ,BCL2 ,cost-effectiveness ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Bruton tyrosine kinase inhibitors (BTKi) and the BCL2 inhibitor venetoclax, with or without the anti-CD20 monoclonal antibody Obinutuzumab, represent the preferred options for the first-line therapy of CLL because they are more effective and may improve quality of life. However, patient inclusion criteria are heterogeneous across trials designed for older patients, and the identification of CLL-specific parameters identifying unfit patients at risk of developing drug-specific adverse events is required to guide treatment choice. Due to inclusion/exclusion criteria in trials, higher discontinuation rates with BTKi were reported in real-world studies, and registry analyses provided useful information on factors predicting earlier discontinuation in a real-world setting. Though targeted agents were shown to be cost-effective treatments in high-income countries, the out-of-pocket expenses may limit accessibility to these drugs, and the overall expenditure for new drugs in CLL is projected to increase substantially, posing an issue for sustainability. This being said, the choice of a finite-duration treatment based on venetoclax-containing regimens or treatment until progression with BTKi is today possible in high-income countries, and the therapy choice drivers are represented by coexisting medical conditions rather than age, patient expectations, logistics, and sustainability.
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- 2023
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6. Predictors of Response to Hydroxyurea and Switch to Ruxolitinib in HU-Resistant Polycythaemia VERA Patients: A Real-World PV-NET Study
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Francesca Palandri, Elena Rossi, Giuseppe Auteri, Massimo Breccia, Simona Paglia, Giulia Benevolo, Elena M. Elli, Francesco Cavazzini, Gianni Binotto, Alessia Tieghi, Mario Tiribelli, Florian H. Heidel, Massimiliano Bonifacio, Novella Pugliese, Giovanni Caocci, Monica Crugnola, Francesco Mendicino, Alessandra D'Addio, Simona Tomassetti, Bruno Martino, Nicola Polverelli, Sara Ceglie, Camilla Mazzoni, Rikard Mullai, Alessia Ripamonti, Bruno Garibaldi, Fabrizio Pane, Antonio Cuneo, Mauro Krampera, Gianpietro Semenzato, Roberto M. Lemoli, Nicola Vianelli, Giuseppe A. Palumbo, Alessandro Andriani, Michele Cavo, Roberto Latagliata, and Valerio De Stefano
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myeloproliferative neoplasms ,polycythemia vera ,hydroxyurea ,ruxolitinib ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients’ triggers for switching to ruxolitinib are uncertain. In a real-world analysis, we evaluated the predictors of response, their impact on the clinical outcomes of CR to HU, and the correlations between partial or no response (PR/NR) and a patient switching to ruxolitinib. Among 563 PV patients receiving HU for ≥12 months, 166 (29.5%) achieved CR, 264 achieved PR, and 133 achieved NR. In a multivariate analysis, the absence of splenomegaly (p = 0.03), pruritus (p = 0.002), and a median HU dose of ≥1 g/day (p < 0.001) remained associated with CR. Adverse events were more frequent with a median HU dose of ≥1 g/day. Overall, 283 PR/NR patients (71.3%) continued HU, and 114 switched to ruxolitinib. In the 449 patients receiving only HU, rates of thrombosis, hemorrhages, progression, and overall survival were comparable among the CR, PR, and NR groups. Many PV patients received underdosed HU, leading to lower CR and toxicity rates. In addition, many patients continued HU despite a PR/NR; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised.
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- 2023
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7. Ruxolitinib discontinuation syndrome: incidence, risk factors, and management in 251 patients with myelofibrosis
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Francesca Palandri, Giuseppe Alberto Palumbo, Elena Maria Elli, Nicola Polverelli, Giulia Benevolo, Bruno Martino, Elisabetta Abruzzese, Mario Tiribelli, Alessia Tieghi, Roberto Latagliata, Francesco Cavazzini, Micaela Bergamaschi, Gianni Binotto, Monica Crugnola, Alessandro Isidori, Giovanni Caocci, Florian Heidel, Novella Pugliese, Costanza Bosi, Daniela Bartoletti, Giuseppe Auteri, Daniele Cattaneo, Luigi Scaffidi, Malgorzata Monica Trawinska, Rossella Stella, Fiorella Ciantia, Fabrizio Pane, Antonio Cuneo, Mauro Krampera, Gianpietro Semenzato, Roberto Massimo Lemoli, Alessandra Iurlo, Nicola Vianelli, Michele Cavo, Massimo Breccia, and Massimiliano Bonifacio
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2021
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8. Treatment-free remission in chronic myeloid leukemia patients treated front-line with nilotinib: 10-year followup of the GIMEMA CML 0307 study
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Gabriele Gugliotta, Fausto Castagnetti, Massimo Breccia, Luciano Levato, Tamara Intermesoli, Mariella D'Adda, Marzia Salvucci, Fabio Stagno, Giovanna Rege-Cambrin, Mario Tiribelli, Bruno Martino, Monica Bocchia, Michele Cedrone, Elena Trabacchi, Francesco Cavazzini, Ferdinando Porretto, Federica Sorà, Maria Pina Simula, Francesco Albano, Simona Soverini, Robin Foà, Fabrizio Pane, Michele Cavo, Giuseppe Saglio, Michele Baccarani, and Gianantonio Rosti
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
We report the final analysis, with a 10-year follow-up, of the phase II study GIMEMA CML 0307 (NCT 00481052), which enrolled 73 adult patients (median age 51 years; range, 18-83) with newly diagnosed chronic-phase chronic myeloid leukemia to investigate the efficacy and the toxicity of front-line treatment with nilotinib. The initial dose was 400 mg twice daily; the dose was reduced to 300 mg twice daily as soon as this dose was approved and registered. The 10-year overall survival and progression- free survival were 94.5%. At the last contact, 36 (49.3%) patients were continuing nilotinib (22 patients at 300 mg twice daily, 14 at lower doses), 18 (24.7%) patients were in treatment-free remission, 14 (19.2%) were receiving other tyrosinekinase inhibitors and four (5.5%) patients have died. The rates of major and deep molecular responses by 10 years were 96% and 83%, respectively. The median times to major and deep molecular response were 6 and 18 months, respectively. After a median duration of nilotinib treatment of 88 months, 24 (32.9%) patients discontinued nilotinib while in stable deep molecular response. In these patients, the 2-year estimated treatment-free survival was 72.6%. The overall treatment-free remission rate, calculated on all enrolled patients, was 24.7% (18/73 patients). Seventeen patients (23.3%), at a median age of 69 years, had at least one arterial obstructive event. In conclusion, the use of nilotinib front-line in chronic phase chronic myeloid leukemia can induce a stable treatment-free remission in a relevant number of patients, although cardiovascular toxicity remains of concern.
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- 2022
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9. Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP
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Michele Baccarani, Elisabetta Abruzzese, Vincenzo Accurso, Francesco Albano, Mario Annunziata, Sara Barulli, Germana Beltrami, Micaela Bergamaschi, Gianni Binotto, Monica Bocchia, Giovanni Caocci, Isabella Capodanno, Francesco Cavazzini, Michele Cedrone, Marco Cerrano, Monica Crugnola, Mariella D'Adda, Chiara Elena, Carmen Fava, Paola Fazi, Claudio Fozza, Sara Galimberti, Valentina Giai, Antonella Gozzini, Gabriele Gugliotta, Alessandra Iurlo, Gaetano La Barba, Luciano Levato, Alessandro Lucchesi, Luigia Luciano, Francesca Lunghi, Monia Lunghi, Michele Malagola, Roberto Marasca, Bruno Martino, Angela Melpignano, Maria Cristina Miggiano, Enrico Montefusco, Caterina Musolino, Fausto Palmieri, Patrizia Pregno, Davide Rapezzi, Giovanna Rege-Cambrin, Serena Rupoli, Marzia Salvucci, Rosaria Sancetta, Simona Sica, Raffaele Spadano, Fabio Stagno, Mario Tiribelli, Simona Tomassetti, Elena Trabacchi, Massimiliano Bonifacio, Massimo Breccia, Fausto Castagnetti, Fabrizio Pane, Domenico Russo, Giuseppe Saglio, Simona Soverini, Paolo Vigneri, and Gianantonio Rosti
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Specialties of internal medicine ,RC581-951 - Abstract
Abstract: Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 ≤10% at 3 months, ≤1% at 6 months, ≤0.1% at 12 months, ≤0.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 >10% at 3 and 6 months, >1% at 12 months, and >0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR.
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- 2019
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10. The complex karyotype landscape in chronic lymphocytic leukemia allows the refinement of the risk of Richter syndrome transformation
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Andrea Visentin, Laura Bonaldi, Gian Matteo Rigolin, Francesca Romana Mauro, Annalisa Martines, Federica Frezzato, Stefano Pravato, Leila Romano Gargarella, Maria Antonella Bardi, Maurizio Cavallari, Eleonora Volta, Francesco Cavazzini, Mauro Nanni, Monica Facco, Francesco Piazza, Anna Guarini, Robin Foà, Gianpietro Semenzato, Antonio Cuneo, and Livio Trentin
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chronic lymphocytic leukemia ,Richter syndrome ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Complex karyotype (CK) at chronic lymphocytic leukemia (CLL) diagnosis is a negative biomarker of adverse outcome. Since the impact of CK and its subtypes, namely type-2 CK (CK with major structural abnormalities) or high-CK (CK with ≥5 chromosome abnormalities), on the risk of developing Richter syndrome (RS) is unknown, we carried out a multicenter real-life retrospective study to test its prognostic impact. Among 540 CLL patients, 107 harbored a CK at CLL diagnosis, 78 were classified as CK2 and 52 as high-CK. Twenty-eight patients developed RS during a median follow-up of 6.7 years. At the time of CLL diagnosis, CK2 and high-CK were more common and predicted the highest risk of RS transformation, together with advanced Binet stage, unmutated (U)-IGHV, 11q-, and TP53 abnormalities. We integrated these variables into a hierarchical model: high-CK and/or CK2 patients showed a 10-year time to RS (TTRS) of 31%; U-IGHV/11q- /TP53 abnormalities/Binet stage B-C patients had a 10-year TTRS of 12%; mutated (M)-IGHV without CK and TP53 disruption a 10-year TTRS of 3% (P
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- 2021
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11. Observational study of chronic myeloid leukemia Italian patients who discontinued tyrosine kinase inhibitors in clinical practice
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Carmen Fava, Giovanna Rege-Cambrin, Irene Dogliotti, Marco Cerrano, Paola Berchialla, Matteo Dragani, Gianantonio Rosti, Fausto Castagnetti, Gabriele Gugliotta, Bruno Martino, Carlo Gambacorti-Passerini, Elisabetta Abruzzese, Chiara Elena, Patrizia Pregno, Antonella Gozzini, Isabella Capodanno, Micaela Bergamaschi, Monica Crugnola, Monica Bocchia, Sara Galimberti, Davide Rapezzi, Alessandra Iurlo, Daniele Cattaneo, Roberto Latagliata, Massimo Breccia, Michele Cedrone, Marco Santoro, Mario Annunziata, Luciano Levato, Fabio Stagno, Francesco Cavazzini, Nicola Sgherza, Valentina Giai, Luigia Luciano, Sabina Russo, Pellegrino Musto, Giovanni Caocci, Federica Sorà, Francesco Iuliano, Francesca Lunghi, Giorgina Specchia, Fabrizio Pane, Dario Ferrero, Michele Baccarani, and Giuseppe Saglio
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
It is judged safe to discontinue treatment with tyrosine kinase inhibitors (TKI) for chronic myeloid leukemia (CML) in experimental trials on treatment-free remission (TFR). We collected a total of 293 Italian patients with chronic phase CML who discontinued TKI in deep molecular response. Seventy-two percent of patients were on treatment with imatinib, and 28% with second generation TKI at the time of discontinuation. Median duration of treatment with the last TKI was 77 months [Interquartile Range (IQR) 54;111], median duration of deep molecular response was 46 months (IQR 31;74). Duration of treatment with TKI and duration of deep molecular response were shorter with second generation TKI than with imatinib (P
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- 2019
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12. A Tangle of Genomic Aberrations Drives Multiple Myeloma and Correlates with Clinical Aggressiveness of the Disease: A Comprehensive Review from a Biological Perspective to Clinical Trial Results
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Mariarosaria Sessa, Francesco Cavazzini, Maurizio Cavallari, Gian Matteo Rigolin, and Antonio Cuneo
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Multiple Myeloma ,genomic aberrations ,clinical trials ,Genetics ,QH426-470 - Abstract
Multiple myeloma (MM) is a genetically heterogeneous disease, in which the process of tumorigenesis begins and progresses through the appearance and accumulation of a tangle of genomic aberrations. Several are the mechanisms of DNA damage in MM, varying from single nucleotide substitutions to complex genomic events. The timing of appearance of aberrations is well studied due to the natural history of the disease, that usually progress from pre-malignant to malignant phase. Different kinds of aberrations carry different prognostic significance and have been associated with drug resistance in some studies. Certain genetic events are well known to be associated with prognosis and are incorporated in risk evaluation in MM at diagnosis in the revised International Scoring System (R-ISS). The significance of some other aberrations needs to be further explained. Since now, few phase 3 randomized trials included analysis on patient’s outcomes according to genetic risk, and further studies are needed to obtain useful data to stratify the choice of initial and subsequent treatment in MM.
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- 2020
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13. Extensive next-generation sequencing analysis in chronic lymphocytic leukemia at diagnosis: clinical and biological correlations
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Gian Matteo Rigolin, Elena Saccenti, Cristian Bassi, Laura Lupini, Francesca Maria Quaglia, Maurizio Cavallari, Sara Martinelli, Luca Formigaro, Enrico Lista, Maria Antonella Bardi, Eleonora Volta, Elisa Tammiso, Aurora Melandri, Antonio Urso, Francesco Cavazzini, Massimo Negrini, and Antonio Cuneo
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Chronic lymphocytic leukemia ,Gene mutation analysis ,Next-generation sequencing ,Complex karyotype ,Prognosis ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background In chronic lymphocytic leukemia (CLL), next-generation sequencing (NGS) analysis represents a sensitive, reproducible, and resource-efficient technique for routine screening of gene mutations. Methods We performed an extensive biologic characterization of newly diagnosed CLL, including NGS analysis of 20 genes frequently mutated in CLL and karyotype analysis to assess whether NGS and karyotype results could be of clinical relevance in the refinement of prognosis and assessment of risk of progression. The genomic DNA from peripheral blood samples of 200 consecutive CLL patients was analyzed using Ion Torrent Personal Genome Machine, a NGS platform that uses semiconductor sequencing technology. Karyotype analysis was performed using efficient mitogens. Results Mutations were detected in 42.0 % of cases with 42.8 % of mutated patients presenting 2 or more mutations. The presence of mutations by NGS was associated with unmutated IGHV gene (p = 0.009), CD38 positivity (p = 0.010), risk stratification by fluorescence in situ hybridization (FISH) (p
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- 2016
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14. 'Hemophagocytic Lymphohistiocytosis after EBV reactivation and ibrutinib treatment in relapsed/refractory Chronic Lymphocytic Leukemia'
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Maurizio Cavallari, Maria Ciccone, Simonetta Falzoni, Francesco Cavazzini, Luca Formigaro, Francesco Di Virgilio, Antonella Rotola, Gian Matteo Rigolin, and Antonio Cuneo
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Hemophagocytic Lymphohisticytosis ,Chronic Lymphocytic Leukemia ,Epstein-barr virus ,Ibrutinib ,Anti-cytokine therapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Hemophagocytic Lymphohistiocytosis (HLH) is a rare syndrome characterized by ineffective T-cell and NK response. We report the clinical course of a patient with relapsed CLL who developed acute symptoms soon after starting ibrutinib. Hyperpyrexia, splenomegaly, hyperferritinemia, hypertriglyceridemia, cytopenias, and a typical cytokine pattern, i.e. high interleukin (IL)−6, IL10 and IL18, were consistent with a diagnosis of HLH. Coexistent Epstein Barr virus reactivation was documented. Ibrutinib-induced impairment of NK degranulation, associated with EBV reactivation and CLL-related immunodeficiency may have contributed to the development of HLH in our patient.
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- 2017
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15. Erratum to: Extensive next-generation sequencing analysis in chronic lymphocytic leukemia at diagnosis: clinical and biological correlations
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Gian Matteo Rigolin, Elena Saccenti, Cristian Bassi, Laura Lupini, Francesca Maria Quaglia, Maurizio Cavallari, Sara Martinelli, Luca Formigaro, Enrico Lista, Maria Antonella Bardi, Eleonora Volta, Elisa Tammiso, Aurora Melandri, Antonio Urso, Francesco Cavazzini, Massimo Negrini, and Antonio Cuneo
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Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2016
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16. Incidence of second primary malignancies and related mortality in patients with imatinib-treated chronic myeloid leukemia
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Gabriele Gugliotta, Fausto Castagnetti, Massimo Breccia, Francesco Albano, Alessandra Iurlo, Tamara Intermesoli, Elisabetta Abruzzese, Luciano Levato, Mariella D’Adda, Patrizia Pregno, Francesco Cavazzini, Fabio Stagno, Bruno Martino, Gaetano La Barba, Federica Sorà, Mario Tiribelli, Catia Bigazzi, Gianni Binotto, Massimiliano Bonifacio, Clementina Caracciolo, Simona Soverini, Robin Foà, Michele Cavo, Giovanni Martinelli, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, and Gianantonio Rosti
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
The majority of patients with chronic myeloid leukemia are successfully managed with life-long treatment with tyrosine kinase inhibitors. In patients in chronic phase, other malignancies are among the most common causes of death, raising concerns on the relationship between these deaths and the off-target effects of tyrosine kinase inhibitors. We analyzed the incidence of second primary malignancies, and related mortality, in 514 chronic myeloid leukemia patients enrolled in clinical trials in which imatinib was given as first-line treatment. We then compared the observed incidence and mortality with those expected in the age- and sex-matched Italian general population, calculating standardized incidence and standardized mortality ratios. After a median follow-up of 74 months, 5.8% patients developed second primary malignancies. The median time from chronic myeloid leukemia to diagnosis of the second primary malignancies was 34 months. We did not find a higher incidence of second primary malignancies compared to that in the age- and sex-matched Italian general population, with standardized incidence ratios of 1.06 (95% CI: 0.57–1.54) and 1.61 (95% CI: 0.92–2.31) in males and females, respectively. Overall, 3.1% patients died of second primary malignancies. The death rate in patients with second primary malignancies was 53% (median overall survival: 18 months). Among females, the observed cancer-related mortality was superior to that expected in the age- and sex-matched Italian population, with a standardized mortality ratio of 2.41 (95% CI: 1.26 – 3.56). In conclusion, our analysis of patients with imatinib-treated chronic myeloid leukemia did not reveal a higher incidence of second primary malignancies; however, the outcome of second primary malignancies in such patients was worse than expected. Clinicaltrials.gov: NCT00514488, NCT00510926.
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- 2017
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17. Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia
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Gabriele Gugliotta, Fausto Castagnetti, Massimo Breccia, Luciano Levato, Mariella D’Adda, Fabio Stagno, Mario Tiribelli, Marzia Salvucci, Carmen Fava, Bruno Martino, Michele Cedrone, Monica Bocchia, Elena Trabacchi, Francesco Cavazzini, Emilio Usala, Antonella Russo Rossi, Maria Teresa Bochicchio, Simona Soverini, Giuliana Alimena, Michele Cavo, Fabrizio Pane, Giovanni Martinelli, Giuseppe Saglio, Michele Baccarani, and Gianantonio Rosti
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Nilotinib is a second-generation tyrosine kinase inhibitor that has been approved for the first-line treatment of chronic-phase chronic myeloid leukemia, based on the results of a prospective randomized study of nilotinib versus imatinib (ENESTnd). Apart from this registration study, very few data are currently available on first-line nilotinib treatment. We report here the long-term, 6-year results of the first investigator-sponsored, GIMEMA multicenter phase 2, single-arm trial with nilotinib 400 mg twice daily as first-line treatment in 73 patients with chronic-phase chronic myeloid leukemia. Six-year overall survival and progression-free survival rates were 96%, with one death after progression to blast phase. At 6 years, 75% of the patients were still on nilotinib. The cumulative incidence of major molecular response was 98%; only one patient had a confirmed loss of major molecular response. The cumulative incidence of deep molecular response (MR 4.0) was 76%. Deep molecular response was stable (≥2 years) in 34% of these patients. Cardiovascular adverse events, mainly due to arterial thrombosis, occurred in 11/73 patients (15%), after 24 to 76 months of therapy. They were more frequent in elderly patients, and in those with baseline cardiovascular risk factors. None was fatal, although there was a relevant morbidity. This is the study with the longest follow-up of a high dose of nilotinib (400 mg twice daily): it highlights the high efficacy and the cardiovascular toxicity of the drug (CTG.NCT.00481052).
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- 2015
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18. Outcome of 82 chronic myeloid leukemia patients treated with nilotinib or dasatinib after failure of two prior tyrosine kinase inhibitors
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Antonella Russo Rossi, Massimo Breccia, Elisabetta Abruzzese, Fausto Castagnetti, Luigiana Luciano, Antonella Gozzini, Mario Annunziata, Bruno Martino, Fabio Stagno, Francesco Cavazzini, Mario Tiribelli, Giuseppe Visani, Patrizia Pregno, Pellegrino Musto, Carmen Fava, Nicola Sgherza, Francesco Albano, Gianantonio Rosti, Giuliana Alimena, and Giorgina Specchia
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
There have been few reports of a response to dasatinib or nilotinib after failure of two prior sequential tyrosine kinase inhibitors. We report the outcome of 82 chronic phase patients who received nilotinib or dasatinib as third-line alternative tyrosine kinase inhibitor therapy. Thirty-four patients failed to respond to nilotinib and were started on dasatinib as third-line tyrosine kinase inhibitor therapy while 48 patients were switched to nilotinib after dasatinib failure. Overall, we obtained a cytogenetic response in 32 of 82 patients and major molecular response in 13 patients; disease progression occurred in 12 patients. At last follow up, 70 patients (85.4%) were alive with a median overall survival of 46 months. Our results show that third-line tyrosine kinase inhibitor therapy in chronic myeloid leukemia patients after failure of two prior sequential tyrosine kinase inhibitors may induce a response that, in some instances, could prolong overall survival and affect event-free survival.
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- 2013
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19. Charlson comorbidity index and adult comorbidity evaluation-27 scores might predict treatment compliance and development of pleural effusions in elderly patients with chronic myeloid leukemia treated with second-line dasatinib
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Massimo Breccia, Roberto Latagliata, Fabio Stagno, Luigiana Luciano, Antonella Gozzini, Fausto Castagnetti, Carmen Fava, Francesco Cavazzini, Mario Annunziata, Antonella Russo Rossi, Patrizia Pregno, Elisabetta Abruzzese, Paolo Vigneri, Giovanna Rege-Cambrin, Simona Sica, Fabrizio Pane, Valeria Santini, Giorgina Specchia, Gianantonio Rosti, and Giuliana Alimena
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Background Comorbidities may affect survival and choice of treatment among cancer patients. In fact, comorbidities have been identified as significant determinants of response to therapy in older patients with acute myeloid leukemia, breast cancer, head and neck cancer, and lung cancer. The Charlson comorbidity index and adult comorbidity evaluation-27 are lists of comorbidities with a weight assigned from 1 to 6 for the former and from 0 to 3 for the latter score, derived from relative risk estimates of a proportional hazard regression model using clinical data.Design and Methods We retrospectively evaluated the Charlson index and adult comorbidity evaluation-27 score in a cohort of 125 elderly (> 60 years) patients with chronic phase chronic myeloid leukemia who received dasatinib after showing resistance or intolerance to imatinib with the aim of establishing associations between comorbidities and the development of pleural effusions or compliance with the drug treatment.Results We found a significant association between the Charlson index as well as the adult comorbidity evaluation-27 score and the rate of drug reduction or suspension: with regards to the Charlson index, 49% of score 0 patients had a dose reduction compared to 63% of patients with score 1, 74% of those with score 2 and 100% of patients with score 3–5 (P=0.03); with regards to the adult comorbidity evaluation-27 score, 45% of patients had score 0–1 and 69% of patients with score 2–3 had a dose reduction. Of the 65 patients with Charlson score 0, 29% had at least one suspension of treatment (79% for hematologic and 21% for non-hematologic toxicity), compared to 46% of patients with score 1 (37% for hematologic and 69% for non-hematologic toxicity), 58% of patients with score 2 (36% for hematologic and 64% for non-hematologic toxicity) and 100% of patients with score 3 or 4 (all patients for both types of toxicity). High adult comorbidity index-27 scores identified patients at high risk of grade 3/4 hematologic toxicity. Forty-one patients (32.8%) experienced pleural effusion during treatment: the highest scores for both indices were associated with an increased risk of pleural effusions.Conclusions In elderly patients with chronic myeloid leukemia treated with dasatinib, the rate of drug reduction or suspension and the incidence of pleural effusions seem to be associated with the presence of comorbidities: stratification according to the Charlson index and adult comorbidity evaluation-27 score before dasatinib therapy may enable the identification of patients at risk of major toxicities.
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- 2011
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20. Ruxolitinib in cytopenic myelofibrosis: Response, toxicity, drug discontinuation, and outcome
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Francesca Palandri, Massimo Breccia, Camilla Mazzoni, Giuseppe Auteri, Elena Maria Elli, Malgorzata M. Trawinska, Nicola Polverelli, Mario Tiribelli, Giulia Benevolo, Alessandra Iurlo, Alessia Tieghi, Florian H. Heidel, Giovanni Caocci, Eloise Beggiato, Gianni Binotto, Francesco Cavazzini, Maurizio Miglino, Costanza Bosi, Monica Crugnola, Monica Bocchia, Bruno Martino, Novella Pugliese, Mattia Biondo, Marta Venturi, Luigi Scaffidi, Alessandro Isidori, Daniele Cattaneo, Mauro Krampera, Fabrizio Pane, Daniela Cilloni, Gianpietro Semenzato, Roberto M. Lemoli, Antonio Cuneo, Elisabetta Abruzzese, Daniela Bartoletti, Simona Paglia, Nicola Vianelli, Michele Cavo, Massimiliano Bonifacio, and Giuseppe A. Palumbo
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Cancer Research ,Oncology ,ruxolitinib ,cytopenia ,myelofibrosis ,myelodepletive phenotype ,myeloproliferative neoplasms - Published
- 2023
21. Choice of Tyrosine Kinase Inhibitor and Early Events during the First Year of Therapy in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia (CML) Patients with Concomitant Diabetes: A 'Campus CML' Study
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Isabella Capodanno, Mario Tiribelli, Maria Cristina Miggiano, Cristina Bucelli, Francesco Cavazzini, Sabrina Leonetti Crescenzi, Sabina Russo, Emilia Scalzulli, Andrea Bernardelli, Luigiana Luciano, Olga Mulas, Giuseppina Loglisci, Chiara Elena, Umberto Pizzano, Immacolata Attolico, Gianni Binotto, Elena Crisà, Paolo Sportoletti, Ambra Di Veroli, Anna Rita Scortechini, Annapaola Leporace, Maria Basile, Monica Crugnola, Fabio Stagno, Pamela Murgano, Davide Rapezzi, Debora Luzi, Alessandra Iurlo, Monica Bocchia, Carmen Fava, Alessandra Malato, Sara Galimberti, Iolanda Donatella Vincelli, Malgorzata Monika Trawinska, Michele Pizzuti, Giovanni Caocci, Massimiliano Bonifacio, Giuseppe Saglio, Giorgina Specchia, Massimo Breccia, and Roberto Latagliata
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
22. Extranodal localization of non-Hodgkin’s lymphoma in systemic sclerosis: A diagnostic challenge and review of the literature
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Giorgio Galoppini, Beatrice Maranini, Giovanni Ciancio, Melissa Padovan, Gian Luca Casoni, Francesco Cavazzini, Roberta Gafà, Giovanni Lanza, and Marcello Govoni
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Rheumatology ,Immunology ,Immunology and Allergy - Abstract
Background: Systemic sclerosis is associated with an increased incidence of malignancies, in particular solid neoplasms. Hematological cancers have been also observed in autoimmune diseases, though rarely present with lung involvement. The latter may be misdiagnosed in systemic sclerosis patients, due to the frequent concomitant interstitial lung disease. Case description: Here, we present the case of a 63-year-old man affected by systemic sclerosis presenting with an atypical lung imaging and splenomegaly, who was diagnosed with splenic marginal zone lymphoma, thus raising the suspicion of lung secondarism. We discuss the diagnostic challenge of differential diagnosis in interstitial lung presentation and briefly review the available literature on this topic. Conclusion: Several reports have demonstrated an increased risk of malignancy in patients with systemic sclerosis. Still, the lack of concretely defined guidelines for systemic sclerosis, along with systemic sclerosis multifaceted organ involvement at presentation, may challenge diagnosis and management. Here, we remark the importance of clinical work-up and a multidisciplinary approach in systemic sclerosis, to early detect and treat concomitant hematological malignancies, especially during the first years of the disease.
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- 2022
23. Peripheral blasts are associated with responses to ruxolitinib and outcomes in patients with chronic‐phase myelofibrosis
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Francesca Palandri, Daniela Bartoletti, Alessandra Iurlo, Massimiliano Bonifacio, Elisabetta Abruzzese, Giovanni Caocci, Elena M. Elli, Giuseppe Auteri, Mario Tiribelli, Nicola Polverelli, Maurizio Miglino, Florian H. Heidel, Alessia Tieghi, Giulia Benevolo, Eloise Beggiato, Carmen Fava, Francesco Cavazzini, Novella Pugliese, Gianni Binotto, Costanza Bosi, Bruno Martino, Monica Crugnola, Emanuela Ottaviani, Giorgia Micucci, Malgorzata M. Trawinska, Antonio Cuneo, Monica Bocchia, Mauro Krampera, Fabrizio Pane, Roberto M. Lemoli, Daniela Cilloni, Nicola Vianelli, Michele Cavo, Giuseppe A. Palumbo, and Massimo Breccia
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myelofibrosis ,outcome ,peripheral blasts ,response ,ruxolitinib ,Cancer Research ,Pyrimidines ,Treatment Outcome ,Oncology ,Primary Myelofibrosis ,Nitriles ,Humans ,Pyrazoles - Abstract
The presence of peripheral blasts (PB) is a negative prognostic factor in patients with primary and secondary myelofibrosis (MF) and PB ≥4% was associated with a particularly unfavorable prognosis. Ruxolitinib (RUX) is the JAK1/2 inhibitor most used for treatment of MF-related splenomegaly and symptoms. Its role has not been assessed in correlation with PB.In 794 chronic-phase MF patients treated with RUX, we evaluated the impact of baseline percentage of PB on response (spleen and symptoms responses) and outcome (RUX discontinuation-free, leukemia-free, and overall survival). Three subgroups were compared: PB-0 (no PB, 61.3%), PB-4 (PB 1%-4%, 33.5%), and PB-9 (PB 5%-9%, 5.2%).At 3 and 6 months, spleen responses were less frequently achieved by PB-4 (P = .001) and PB-9 (P = .004) compared to PB-0 patients. RUX discontinuation-free, leukemia-free, and overall survival were also worse for PB-4 and PB-9 patients (P = .001, P = .002, and P.001, respectively).Personalized approaches beyond RUX monotherapy may be useful in PB-4 and particularly in PB-9 patients.
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- 2022
24. Permanent Discontinuation of Tyrosine Kinase Inhibitor Frontline Therapy in Patients with Chronic Phase Chronic Myeloid Leukemia Patients during the First 36 Months of Treatment: A 'Campus CML' Study
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Roberto Latagliata, Isabella Capodanno, Maria Cristina Miggiano, Alessandra Iurlo, Francesco Cavazzini, Sabrina Leonetti Crescenzi, Sabina Russo, Ida Carmosino, Andrea Bernardelli, Olga Mulas, Chiara Elena, Gianni Binotto, Elena Crisà, Ambra Di Veroli, Anna Rita Scortechini, Maria Basile, Monica Crugnola, Pamela Murgano, Michele Pizzuti, Cristina Bucelli, Carmen Fava, Matteo Dalmazzo, Francesca Lunghi, Giovanni Caocci, Massimiliano Bonifacio, Giuseppe Saglio, Giorgina Specchia, Massimo Breccia, and Mario Tiribelli
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
25. Impact of comorbidities and body mass index on the outcome of polycythemia vera patients
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Alessia Tieghi, Alessandra D'Addio, Florian H. Heidel, Roberto Latagliata, Elisa Bossi, Francesco Cavazzini, Giulia Benevolo, Nicola Vianelli, Michele Cavo, Roberto M. Lemoli, Mauro Krampera, Massimo Breccia, Massimiliano Bonifacio, Gianni Binotto, Antonio Cuneo, Giovanni Caocci, Daniela Bartoletti, Mario Tiribelli, Ida Carmosino, Lucia Catani, Giuseppe Auteri, Francesco Lanza, Giuseppe A. Palumbo, Nicola Polverelli, Francesca Palandri, Micaela Bergamaschi, Monica Crugnola, Elena Maria Elli, Benevolo G., Elli E.M., Bartoletti D., Latagliata R., Tiribelli M., Heidel F.H., Cavazzini F., Bonifacio M., Crugnola M., Binotto G., D'Addio A., Tieghi A., Bergamaschi M., Caocci G., Polverelli N., Bossi E., Auteri G., Carmosino I., Catani L., Cuneo A., Krampera M., Lanza F., Lemoli R.M., Vianelli N., Breccia M., Palumbo G.A., Cavo M., and Palandri F.
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Male ,Cancer Research ,Comorbidity ,Overweight ,Primary Myelofibrosi ,0302 clinical medicine ,Retrospective Studie ,Risk Factors ,body mass index ,cancer ,Charlson comorbidity index ,outcome ,polycythemia vera ,thrombotic risk ,80 and over ,Cumulative incidence ,Aged, 80 and over ,Incidence ,Incidence (epidemiology) ,Hazard ratio ,Hematology ,General Medicine ,Middle Aged ,Oncology ,030220 oncology & carcinogenesis ,Thrombosi ,Female ,Underweight ,medicine.symptom ,Human ,Adult ,medicine.medical_specialty ,NO ,Follow-Up Studie ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Aged ,Retrospective Studies ,business.industry ,Risk Factor ,Thrombosis ,Retrospective cohort study ,medicine.disease ,Follow-Up Studies ,Polycythemia Vera ,Primary Myelofibrosis ,Body Mass Index ,Body Mass Index, Cancer ,Charlson Comorbidity Index, Outcome, Polycythemia Vera, Thrombotic risk ,business ,Body mass index ,030215 immunology - Abstract
In 816 patients with 2016 World Health Organization-defined polycythemia vera (PV) enrolled in a multicenter retrospective study, we investigated the predictive value of Charlson comorbidity index (CCI) and body mass index (BMI) on thrombosis, progression to post-PV myelofibrosis (PPV-MF) and survival. Patients were subgrouped according to CCI=0 (58.1%, no comorbidities) or CCI≥1 (41.9%) and according to normal/underweight (BMI 
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- 2021
26. Impact of comorbidities and body mass index in patients with myelofibrosis treated with ruxolitinib
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Daniele Cattaneo, Nicola Sgherza, Roberto Latagliata, Francesco Cavazzini, Renato Fanin, Antonio Cuneo, Giuseppe A. Palumbo, Alessia Tieghi, Nicola Vianelli, Gianpietro Semenzato, Gianni Binotto, Robin Foà, Matteo Molica, Mariella D'Adda, Roberto M. Lemoli, Francesca Palandri, Michele Cavo, Daniela Bartoletti, Alessandra Iurlo, Massimo Breccia, Elisabetta Abruzzese, Nicola Polverelli, Domenico Russo, Giuseppe Auteri, Mario Tiribelli, Florian H. Heidel, Lucia Catani, Costanza Bosi, Alessandro Isidori, Luigi Scaffidi, Franco Aversa, Micaela Bergamaschi, Massimiliano Bonifacio, Monica Crugnola, Massimo Breccia, Daniela Bartoletti, Massimiliano Bonifacio, Giuseppe A. Palumbo, Nicola Polverelli, Elisabetta Abruzzese, Micaela Bergamaschi, Alessia Tieghi, Mario Tiribelli, Alessandra Iurlo, Francesco Cavazzini, Nicola Sgherza, Gianni Binotto, Alessandro Isidori, Mariella D’Adda, Monica Crugnola, Costanza Bosi, Florian Heidel, Matteo Molica, Luigi Scaffidi, Daniele Cattaneo, Roberto Latagliata, Giuseppe Auteri, Roberto M. Lemoli, Renato Fanin, Domenico Russo, Franco Aversa, Antonio Cuneo, Gianpietro Semenzato, Lucia Catani, Michele Cavo, Nicola Vianelli, Robin Foà, and Francesca Palandri
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Male ,Ruxolitinib ,Time Factors ,Myelofibrosis ,BMI ,CCI ,Comorbidities ,Adult ,Age Factors ,Aged ,Aged, 80 and over ,Disease-Free Survival ,Female ,Humans ,Middle Aged ,Primary Myelofibrosis ,Pyrazoles ,Sex ,Sex Factors ,Survival Rate ,Body Mass Index ,Gastroenterology ,0302 clinical medicine ,80 and over ,Hematology ,Myelofibrosi ,General Medicine ,030220 oncology & carcinogenesis ,Cohort ,BMI, CCI, Comorbidities, Myelofibrosis, Ruxolitinib ,Comorbiditie ,Underweight ,medicine.symptom ,medicine.drug ,medicine.medical_specialty ,Anemia ,NO ,03 medical and health sciences ,Internal medicine ,Nitriles ,medicine ,Survival rate ,business.industry ,medicine.disease ,Pyrimidines ,business ,Body mass index ,030215 immunology - Abstract
Comorbidities defined by the Charlson comorbidity index (CCI) and body mass index (BMI) are significantly associated with outcome in patients who receive continuous treatment with tyrosine kinase inhibitors. We evaluated the impact of CCI and BMI on responses, drug-related toxicities, and outcome in a cohort of 402 patients with myelofibrosis (MF) treated with ruxolitinib in 23 European Hematology Centers. Comorbidities were evaluable in all 402 patients. A higher (≥ 3) CCI did not correlate with a lower spleen reduction at any time (p = 0.68) or symptoms' response (p = 0.11), but influenced the onset of anemia during the first 3months of treatment and later (p = 0.02 and p = 0.03, respectively) in patients without anemia baseline. BMI was evaluable in 380 patients and did not correlate with differences in spleen and symptoms response (p = 0.57 and p = 0.49, respectively). A higher CCI and a lower BMI correlated also with a reduced overall survival (p
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- 2018
27. COVID-19 infection in chronic myeloid leukaemia after oneyear of the pandemic in Italy. A Campus CML report
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Elisabetta Abruzzese, Sabina Russo, Carmen Fava, Francesca Lunghi, Sabrina Leonetti Crescenzi, Chiara Elena, Vincenzo Accurso, Fausto Castagnetti, Debora Luzi, Giovanni Caocci, Elena Crisà, Maria Cristina Miggiano, Massimo Breccia, Antonella Gozzini, Giuseppina Loglisci, Giovanna Rege-Cambrin, Monica Bocchia, Immacolata Attolico, Massimiliano Bonifacio, Luigiana Luciano, Gaetano La Barba, Gianantonio Rosti, Maria Stella De Candia, Roberto Latagliata, Gabriele Gugliotta, Francesco Cavazzini, Rosaria Sancetta, Micaela Bergamaschi, Anna Rita Scortechini, Sara Galimberti, Tamara Intermesoli, Federica Sorà, Luciano Levato, Paolo Sportoletti, Monica Crugnola, Mario Tiribelli, Isabella Capodanno, Giuseppe Saglio, Davide Rapezzi, Robin Foà, Alessandra Iurlo, Alessandro Lucchesi, Michele Pizzuti, Sara Barulli, Fabio Stagno, Patrizia Pregno, Alessandra Malato, Gianni Binotto, Agostino Tafuri, Breccia M., Abruzzese E., Accurso V., Attolico I., Barulli S., Bergamaschi M., Binotto G., Bocchia M., Bonifacio M., Caocci G., Capodanno I., Castagnetti F., Cavazzini F., Crisa E., Crugnola M., Stella De Candia M., Elena C., Fava C., Galimberti S., Gozzini A., Gugliotta G., Intermesoli T., Iurlo A., La Barba G., Latagliata R., Leonetti Crescenzi S., Levato L., Loglisci G., Lucchesi A., Luciano L., Lunghi F., Luzi D., Malato A., Cristina Miggiano M., Pizzuti M., Pregno P., Rapezzi D., Rege-Cambrin G., Rosti G., Russo S., Sancetta R., Rita Scortechini A., Sora F., Sportoletti P., Stagno F., Tafuri A., Tiribelli M., Foa R., and Saglio G.
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Male ,Tyrosine-kinase inhibitor ,law.invention ,law ,Retrospective Studie ,Pandemic ,Chronic ,Covid‐19 ,Leukemia ,Mortality rate ,Hematology ,Middle Aged ,Intensive care unit ,Research Papers ,Survival Rate ,Italy ,covid-19 ,Hematologic Neoplasms ,Cohort ,Female ,prognosi ,Human ,Research Paper ,chronic myeloid leukemia, Covid-19, prognosis, mortality ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,medicine.drug_class ,chronic myeloid leukemia ,prognosis, mortality ,Chronic myeloid leukaemia ,Disease-Free Survival ,NO ,Internal medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Covid-19 ,mortality ,prognosis ,Aged ,Humans ,Retrospective Studies ,COVID-19 ,Pandemics ,SARS-CoV-2 ,medicine ,business.industry ,Concomitant ,Commentary ,BCR-ABL Positive ,business ,Myelogenous - Abstract
Limited information is available on the impact of the COVID-19 pandemic on the management of chronic myeloid leukaemia (CML). The Campus CML network collected retrospective information on 8665 CML patients followed at 46 centres throughout Italy during the pandemic between February 2020 and January 2021. Within this cohort, we recorded 217 SARS-CoV-2-positive patients (2·5%). Most patients (57%) were diagnosed as having SARS-CoV-2 infection during the second peak of the pandemic (September 2020 to January 2021). The majority (35%) was aged between 50 and 65years with a male prevalence (73%). Fifty-six percent of patients presented concomitant comorbidities. The median time from CML diagnosis to SARS-CoV-2 infection was six years (three months to 18years). Twenty-one patients (9·6%) required hospitalization without the need of respiratory assistance, 18 (8·2%) were hospitalized for respiratory assistance, 8 (3·6%) were admitted to an intensive care unit, while 170 (78%) were only quarantined. Twenty-three percent of patients discontinued tyrosine kinase inhibitor (TKI) therapy during the infection. Twelve patients died due to COVID-19 with a mortality rate of 5·5% in the positive cohort and of 0·13% in the whole cohort. We could also document sequelae caused by the SARS-CoV-2 infection and an impact of the pandemic on the overall management of CML patients.
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- 2022
28. The complex karyotype landscape in chronic lymphocytic leukemia allows to refine the risk of Richter syndrome transformation
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Francesca Romana Mauro, Francesco Piazza, Francesco Cavazzini, Gianpietro Semenzato, Gian Matteo Rigolin, Laura Bonaldi, Eleonora Volta, Maria Antonella Bardi, Antonio Cuneo, Mauro Nanni, Stefano Pravato, Annalisa Martines, Maurizio Cavallari, Federica Frezzato, Monica Facco, Andrea Visentin, Robin Foà, Leila Romano Gargarella, Livio Trentin, and Anna Guarini
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Oncology ,Richter syndrome ,medicine.medical_specialty ,complex karyotype ,Lymphoma ,Adverse outcomes ,Chronic lymphocytic leukemia ,Karyotype ,Humans ,Mutation ,Retrospective Studies ,Leukemia, Lymphocytic, Chronic, B-Cell ,Lymphoma, Large B-Cell, Diffuse ,NO ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Complex Karyotype ,Large B-Cell ,medicine ,Chronic ,Stage (cooking) ,Leukemia ,business.industry ,B-Cell ,Retrospective cohort study ,Hematology ,medicine.disease ,Diffuse ,Lymphocytic ,Richter's transformation ,Prognostic model ,Biomarker (medicine) ,chronic lymphocytic leukemia ,business ,030215 immunology - Abstract
Complex karyotype (CK) at chronic lymphocytic leukemia (CLL) diagnosis is a negative biomarker of adverse outcome. Since the impact of CK and its subtypes, namely type-2 CK (CK with major structural abnormalities) or high-CK (CK with ≥5 chromosome abnormalities), on the risk of developing Richter syndrome (RS) is unknown, we carried out a multicenter real-life retrospective study to test its prognostic impact. Among 540 CLL patients, 107 harbored a CK at CLL diagnosis, 78 were classified as CK2 and 52 as high-CK. Twenty-eight patients developed RS during a median follow-up of 6.7 years. At the time of CLL diagnosis, CK2 and high-CK were more common and predicted the highest risk of RS transformation, together with advanced Binet stage, unmutated (U)-IGHV, 11q-, and TP53 abnormalities. We integrated these variables into a hierarchical model: high-CK and/or CK2 patients showed a 10-year time to RS (TTRS) of 31%; U-IGHV/11q- /TP53 abnormalities/Binet stage B-C patients had a 10-year TTRS of 12%; mutated (M)-IGHV without CK and TP53 disruption a 10-year TTRS of 3% (P
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- 2022
29. The combination of complex karyotype subtypes and IGHV mutational status identifies new prognostic and predictive groups in chronic lymphocytic leukaemia
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Francesca Romana Mauro, Gian Matteo Rigolin, Silvia Imbergamo, Andrea Visentin, Edoardo Scomazzon, Livio Trentin, Monica Facco, Maurizio A. Nanni, Ilaria Del Giudice, Robin Foà, Francesco Cavazzini, Eleonora Volta, Federica Frezzato, Maria Antonella Bardi, Laura Bonaldi, Antonio Cuneo, Stefano Pravato, Annalisa Martines, Maurizio Cavallari, Gianpietro Semenzato, and Anna Guarini
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Male ,Oncology ,Chronic lymphocytic leukaemia ,Cancer Research ,medicine.medical_specialty ,Karyotype ,Disease ,Predictive markers ,Article ,NO ,Prognostic markers ,03 medical and health sciences ,0302 clinical medicine ,Chemoimmunotherapy ,Internal medicine ,Complex Karyotype ,medicine ,Humans ,Aged ,Aged, 80 and over ,Chromosome Banding ,Female ,Immunoglobulin Heavy Chains ,Leukemia, Lymphocytic, Chronic, B-Cell ,Middle Aged ,Prognosis ,Retrospective Studies ,Chromosome Aberrations ,Mutation ,Mutational status ,business.industry ,Chronic lymphocytic leukemia, complex karyoptype, prognosis ,Retrospective cohort study ,medicine.disease ,Leukemia ,030220 oncology & carcinogenesis ,Chronic lymphocytic leukemia ,complex karyoptype ,prognosis ,IGHV@ ,business - Abstract
Background Complex karyotype (CK) is a heterogeneous category with a negative impact in chronic lymphocytic leukaemia (CLL). Our group has recently reported that CK patients with major structural abnormalities (i.e. CK2) are characterised by a worse prognosis, as compared to other lesions within CK(CK1). Methods We performed a multicentre retrospective study to test whether the combination of CK subtypes with IGHV status could be a relevant prognostic and predictive tool. Results Among 522 patients 13% harboured CK2, 41% CK1 and/or U-IGHV (U-CK1) and 46% M-IGHV without any CK subtypes (M-noCK). After a median follow-up of 5.8 years, CK2 patients had the shortest TTFT (5-year TTFT 31%, 39 and 81%, p
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- 2019
30. Ruxolitinib rechallenge in resistant or intolerant patients with myelofibrosis: Frequency, therapeutic effects, and impact on outcome
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Costanza Bosi, Nicola Vianelli, Fabrizio Pane, Giovanni Caocci, Massimiliano Bonifacio, Mario Tiribelli, Michele Cavo, Malgorzata Monika Trawinska, Daniela Bartoletti, Mauro Krampera, Giuseppe Auteri, Giulia Benevolo, Bruno Martino, Daniele Cattaneo, Roberto M. Lemoli, Giuseppe A. Palumbo, Nicola Polverelli, Massimo Breccia, Luigi Scaffidi, Monica Crugnola, Elisabetta Abruzzese, Antonio Cuneo, Florian H. Heidel, Elena Maria Elli, Elena Masselli, Francesca Palandri, Roberto Latagliata, Francesco Cavazzini, Alessandra Iurlo, Novella Pugliese, Rossella Stella, Giorgia Micucci, Alessia Tieghi, Gianpietro Semenzato, Gianni Binotto, Palandri F., Tiribelli M., Breccia M., Bartoletti D., Elli E.M., Benevolo G., Martino B., Cavazzini F., Tieghi A., Iurlo A., Abruzzese E., Pugliese N., Binotto G., Caocci G., Auteri G., Cattaneo D., Trawinska M.M., Stella R., Scaffidi L., Polverelli N., Micucci G., Masselli E., Crugnola M., Bosi C., Heidel F.H., Latagliata R., Pane F., Cuneo A., Krampera M., Semenzato G., Lemoli R.M., Cavo M., Vianelli N., Bonifacio M., and Palumbo G.A.
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Cancer Research ,medicine.medical_specialty ,Disease status ,Ruxolitinib ,ruxolitinib ,rechallenge ,myelofibrosis ,NO ,03 medical and health sciences ,0302 clinical medicine ,myelofibrosi ,Internal medicine ,Nitriles ,Overall survival ,Medicine ,cancer ,Humans ,In patient ,030212 general & internal medicine ,Myelofibrosis ,Retrospective Studies ,outcome ,business.industry ,Therapeutic effect ,Retrospective cohort study ,medicine.disease ,Discontinuation ,Pyrimidines ,Treatment Outcome ,Oncology ,Primary Myelofibrosis ,030220 oncology & carcinogenesis ,Pyrazoles ,business ,medicine.drug - Abstract
BACKGROUND: After ruxolitinib discontinuation, the outcome of patients with myelofibrosis (MF) is poor with scarce therapeutic possibilities. METHODS: The authors performed a subanalysis of an observational, retrospective study (RUX-MF) that included 703 MF patients treated with ruxolitinib to investigate 1) the frequency and reasons for ruxolitinib rechallenge, 2) its therapeutic effects, and 3) its impact on overall survival. RESULTS: A total of 219 patients (31.2%) discontinued ruxolitinib for ≥14 days and survived for ≥30 days. In 60 patients (27.4%), ruxolitinib was rechallenged for ≥14 days (RUX-again patients), whereas 159 patients (72.6%) discontinued it permanently (RUX-stop patients). The baseline characteristics of the 2 cohorts were comparable, but discontinuation due to a lack/loss of spleen response was lower in RUX-again patients (P =.004). In comparison with the disease status at the first ruxolitinib stop, at its restart, there was a significant increase in patients with large splenomegaly (P 10 mg twice daily predicted better spleen (P =.05) and symptom improvements (P =.02), the reasons for/duration of ruxolitinib discontinuation and the use of other therapies before rechallenge were not associated with rechallenge efficacy. At 1 and 2 years, 33.3% and 48.3% of RUX-again patients, respectively, had permanently discontinued ruxolitinib. The median overall survival was 27.9 months, and it was significantly longer for RUX-again patients (P =.004). CONCLUSIONS: Ruxolitinib rechallenge was mainly used in intolerant patients; there were clinical improvements and a possible survival advantage in many cases, but there was a substantial rate of permanent discontinuation. Ruxolitinib rechallenge should be balanced against newer therapeutic possibilities.
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- 2021
31. Author response for 'EFFICACY OF IDELALISIB AND RITUXIMAB IN RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA TREATED OUTSIDE OF CLINICAL TRIALS. A REPORT OF THE GIMEMA WORKING GROUP'
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null Gian Matteo Rigolin, null Francesco Cavazzini, null Alfonso Piciocchi, null Valentina Arena, null Andrea Visentin, null Gianluigi Reda, null Giulia Zamprogna, null Francesca Cibien, null Orsola Vitagliano, null Marta Coscia, null Lucia Farina, null Gianluca Gaidano, null Roberta Murru, null Marzia Varettoni, null Rossella Paolini, null Paolo Sportoletti, null Daniela Pietrasanta, null Anna Lia Molinari, null Francesca M. Quaglia, null Luca Laurenti, null Roberto Marasca, null Monia Marchetti, null Francesca R. Mauro, null Enrico Crea, null Marco Vignetti, null Massimo Gentile, null Marco Montillo, null Robin Foà, null Antonio Cuneo, and null GIMEMA group
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Clinical trial ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Chronic lymphocytic leukemia ,Relapsed refractory ,Medicine ,Rituximab ,business ,Idelalisib ,medicine.disease ,medicine.drug - Published
- 2021
32. Making Treatment-Free Remission (TFR) Easier in Chronic Myeloid Leukemia: Fact-Checking and Practical Management Tools
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Maria Cristina Miggiano, Marzia Salvucci, Massimiliano Bonifacio, Elisabetta Calistri, Monica Poggiaspalla, Gianni Binotto, Atto Billio, Claudia Minotto, Alessandro Lucchesi, Elena Trabacchi, Francesco Cavazzini, Anna Merli, Mauro Krampera, Sara Galimberti, Antonella Gozzini, Isabella Capodanno, Gabriele Gugliotta, Barbara Scappini, Mario Tiribelli, Gianantonio Rosti, Monica Crugnola, Fausto Castagnetti, Castagnetti F., Binotto G., Capodanno I., Billio A., Calistri E., Cavazzini F., Crugnola M., Gozzini A., Gugliotta G., Krampera M., Lucchesi A., Merli A., Miggiano M.C., Minotto C., Poggiaspalla M., Salvucci M., Scappini B., Tiribelli M., Trabacchi E., Rosti G., Galimberti S., and Bonifacio M.
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Cancer Research ,medicine.medical_specialty ,Standard of care ,Fact checking ,Socio-culturale ,Disease ,chronic-phase chronic myeloid leukemia, tyrosine kinase inhibitors, treatment-free remission ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Early prediction ,medicine ,Humans ,Pharmacology (medical) ,Intensive care medicine ,Protein Kinase Inhibitors ,business.industry ,Remission Induction ,Therapy in Practice ,Myeloid leukemia ,Female sex ,Prognosis ,Discontinuation ,Treatment Outcome ,Oncology ,Disease risk ,Female ,business - Abstract
In chronic-phase chronic myeloid leukemia (CML), tyrosine kinase inhibitors (TKIs) are the standard of care, and treatment-free remission (TFR) following the achievement of a stable deep molecular response (DMR) has become, alongside survival, a primary goal for virtually all patients. The GIMEMA CML working party recently suggested that the possibility of achieving TFR cannot be denied to any patient, and proposed specific treatment policies according to the patient’s age and risk. However, other international recommendations (including 2020 ELN recommendations) are more focused on survival and provide less detailed suggestions on how to choose first and subsequent lines of treatment. Consequently, some grey areas remain. After literature review, a panel of Italian experts discussed the following controversial issues: (1) early prediction of DMR and TFR: female sex, non-high disease risk score, e14a2 transcript and early MR achievement have been associated with stable DMR, but the lack of these criteria is not sufficient to exclude any patient from TFR; (2) criteria for first and subsequent line therapy choice: a number of patient and drug characteristics have been proposed to make a personalized decision; (3) monitoring of residual disease after discontinuation: after the first 6 months, the frequency of molecular tests can be reduced based on MR4.5 persistence and short turnaround time; (4) prognosis of TFR: therapy and DMR duration are important to predict TFR; although immunological control of CML plays a role, no immunological predictive phenotype is currently available. This guidance is intended as a practical tool to support physicians in decision making.
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- 2021
33. Optimal Management of Chronic Lymphocytic Leukemia and Economic Constraints
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Gian Matteo Rigolin, Francesco Cavazzini, Antonio Cuneo, Robin Foà, and Maurizio Cavallari
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Cancer Research ,medicine.medical_specialty ,Randomization ,Chronic lymphocytic leukemia ,Salvage treatment ,Antineoplastic Agents ,value-based pricing ,NO ,Chemoimmunotherapy ,Economic constraints ,Medicine ,Humans ,In patient ,Chronic ,Intensive care medicine ,Leukemia ,venetoclax ,business.industry ,B-Cell ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Optimal management ,Lymphocytic ,BTK inhibitors ,Oncology ,Mutation ,chronic lymphocytic leukemia ,Immunotherapy ,fixed-duration treatment ,IGHV@ ,business - Abstract
In this article, we carry out an overview on the management options available for chronic lymphocytic leukemia (CLL) patients and discuss possible treatment decisions, taking into account the issue of sustainability and availability. Targeted agents have shown to be superior compared with chemoimmunotherapy (CIT) in terms of progression-free survival in high-risk CLL. In the majority of studies, however, continuous treatment was compared with fixed-duration CIT and no overall survival or progression-free survival-2 (time from randomization to second progression or death) advantage could be documented. Meanwhile, a substantial financial burden on both patients and payers has raised issues about affordability and adherence to treatment. Therefore, value-based pricing of new drugs has been used to set up price negotiation policies in several countries, and fixed-duration therapy has shown to be less costly than continuous treatment. Thus, CIT continues to have a role in the treatment of CLL patients with a favorable genetic profile, that is, with a mutated IGHV gene profile and a wild-type TP53. Targeted treatment represents the preferred choice in patients with an unmutated IGHV gene configuration and/or a TP53 disruption, provided that adherence to treatment is guaranteed and bearing in mind that should costly drugs not be available for frontline treatment, new agents can be very effective as first salvage treatment.
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- 2021
34. In chronic lymphocytic leukaemia, SLAMF1 deregulation is associated with genomic complexity and independently predicts a worse outcome
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Antonio Urso, Massimo Negrini, Francesco Rotondo, Aurora Melandri, Elisa Tammiso, Christian Bassi, Antonio Cuneo, Francesco Cavazzini, Maria Antonella Bardi, Marika Rossini, Anita Betulla, Lucia Tognolo, Elena Saccenti, Maurizio Cavallari, and Gian Matteo Rigolin
- Subjects
Adult ,Male ,medicine.medical_specialty ,CD38 ,Gastroenterology ,Disease-Free Survival ,NO ,03 medical and health sciences ,0302 clinical medicine ,International Prognostic Index ,Downregulation and upregulation ,Signaling Lymphocytic Activation Molecule Family Member 1 ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Stage (cooking) ,Chronic lymphocytic leukemia, SLAMF1, prognosis ,Aged ,Chromosome Aberrations ,Lymphocytic leukaemia ,business.industry ,Beta-2 microglobulin ,Karyotype ,Hematology ,Middle Aged ,Leukemia, Lymphocytic, Chronic, B-Cell ,Neoplasm Proteins ,Survival Rate ,030220 oncology & carcinogenesis ,Female ,Chronic lymphocytic leukemia ,prognosis ,IGHV@ ,business ,SLAMF1 ,030215 immunology - Abstract
In a series of 349 patients with chronic lymphocytic leukaemia (CLL), we found lower levels of signalling lymphocytic activation molecule family member 1 (SLAMF1) expression in cases with highly complex karyotypes, as defined by the presence of five or more chromosomal abnormalities (CK5; P < 0·001) and with major chromosomal structural abnormalities (P < 0·001). SLAMF1 downregulation was significantly associated with advanced Binet Stage (P = 0·001), CD38 positivity (P < 0·001), high β2 -microglobulin levels (P < 0·001), immunoglobulin heavy chain variable region gene (IGHV) unmutated status (P < 0·001), 11q deletion (P < 0·001), tumour protein p53 (TP53) disruption (P = 0·011) and higher risk CLL International Prognostic Index categories (P < 0·001). Multivariate analysis showed that downregulated SLAMF1 levels had independent negative prognostic impact on time-to-first treatment (P < 0·001) and overall survival (P < 0·001).
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- 2021
35. A Tangle of Genomic Aberrations Drives Multiple Myeloma and Correlates with Clinical Aggressiveness of the Disease: A Comprehensive Review from a Biological Perspective to Clinical Trial Results
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Francesco Cavazzini, Gian Matteo Rigolin, Maurizio Cavallari, Mariarosaria Sessa, and Antonio Cuneo
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,lcsh:QH426-470 ,Drug Resistance ,Disease ,Drug resistance ,Review ,medicine.disease_cause ,Multiple Myeloma, clinical trials, genomic aberrations ,Tangle ,law.invention ,NO ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Genetics ,Medicine ,Humans ,Genetics (clinical) ,Multiple myeloma ,Randomized Controlled Trials as Topic ,clinical trials ,business.industry ,Genetic heterogeneity ,genomic aberrations ,Genomics ,medicine.disease ,Prognosis ,Clinical trial ,lcsh:Genetics ,030104 developmental biology ,Clinical Trials, Phase III as Topic ,030220 oncology & carcinogenesis ,business ,Carcinogenesis ,Multiple Myeloma ,DNA Damage - Abstract
Multiple myeloma (MM) is a genetically heterogeneous disease, in which the process of tumorigenesis begins and progresses through the appearance and accumulation of a tangle of genomic aberrations. Several are the mechanisms of DNA damage in MM, varying from single nucleotide substitutions to complex genomic events. The timing of appearance of aberrations is well studied due to the natural history of the disease, that usually progress from pre-malignant to malignant phase. Different kinds of aberrations carry different prognostic significance and have been associated with drug resistance in some studies. Certain genetic events are well known to be associated with prognosis and are incorporated in risk evaluation in MM at diagnosis in the revised International Scoring System (R-ISS). The significance of some other aberrations needs to be further explained. Since now, few phase 3 randomized trials included analysis on patient’s outcomes according to genetic risk, and further studies are needed to obtain useful data to stratify the choice of initial and subsequent treatment in MM.
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- 2020
36. Ruxolitinib discontinuation syndrome: incidence, risk factors, and management in 251 patients with myelofibrosis
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Bruno Martino, Daniele Cattaneo, Florian H. Heidel, Elisabetta Abruzzese, Gianni Binotto, Rossella Stella, Giulia Benevolo, Michele Cavo, Micaela Bergamaschi, Roberto Latagliata, Francesco Cavazzini, Novella Pugliese, Massimo Breccia, Alessandro Isidori, Gianpietro Semenzato, Daniela Bartoletti, Mauro Krampera, Malgorzata Monica Trawinska, Costanza Bosi, Giovanni Caocci, Fabrizio Pane, Alessia Tieghi, Francesca Palandri, Roberto M. Lemoli, Elena Maria Elli, Antonio Cuneo, Fiorella Ciantia, Alessandra Iurlo, Monica Crugnola, Giuseppe Auteri, Mario Tiribelli, Massimiliano Bonifacio, Nicola Vianelli, Luigi Scaffidi, Giuseppe A. Palumbo, Nicola Polverelli, Palandri F., Palumbo G.A., Elli E.M., Polverelli N., Benevolo G., Martino B., Abruzzese E., Tiribelli M., Tieghi A., Latagliata R., Cavazzini F., Bergamaschi M., Binotto G., Crugnola M., Isidori A., Caocci G., Heidel F., Pugliese N., Bosi C., Bartoletti D., Auteri G., Cattaneo D., Scaffidi L., Trawinska M.M., Stella R., Ciantia F., Pane F., Cuneo A., Krampera M., Semenzato G., Lemoli R.M., Iurlo A., Vianelli N., Cavo M., Breccia M., and Bonifacio M.
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Ruxolitinib ,medicine.medical_specialty ,Humans ,Janus Kinases ,Multivariate Analysis ,Primary Myelofibrosis ,Protein Kinase Inhibitors ,Pyrazoles ,Risk Factors ,Treatment Outcome ,medicine.medical_treatment ,Splenectomy ,lcsh:RC254-282 ,Nitriles ,Pyrimidines ,Ruxolitinib discontinuation syndrome, risk factors, myelofibrosis ,NO ,Myeloproliferative disease ,Internal medicine ,Correspondence ,medicine ,Risk factor ,Bone pain ,Myelofibrosis ,Respiratory distress ,business.industry ,Incidence (epidemiology) ,Hematology ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Discontinuation ,Oncology ,medicine.symptom ,business ,Haematological diseases ,medicine.drug - Abstract
No abstract available
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- 2020
37. Risk factors for progression to blast phase and outcome in 589 patients with myelofibrosis treated with ruxolitinib: Real-world data
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Massimo Breccia, Mauro Krampera, Alessandro Isidori, Monica Crugnola, Daniela Bartoletti, Elena Maria Elli, Alessia Tieghi, Massimiliano Bonifacio, Micaela Bergamaschi, Costanza Bosi, Roberto Latagliata, Roberto M. Lemoli, Francesco Cavazzini, Florian H. Heidel, Michele Cavo, Nicola Polverelli, Malgorzata Monika Trawinska, Francesca Palandri, Bruno Martino, Daniele Cattaneo, Giulia Benevolo, Giuseppe Auteri, Elisabetta Abruzzese, Gianni Binotto, Alessandra Iurlo, Nicola Vianelli, Antonio Cuneo, Francesco Di Raimondo, Dorian Forte, Davide Griguolo, Gianpietro Semenzato, Giuseppe A. Palumbo, Mario Tiribelli, Palandri F., Breccia M., Tiribelli M., Bonifacio M., Benevolo G., Iurlo A., Elli E.M., Binotto G., Tieghi A., Polverelli N., Martino B., Abruzzese E., Bergamaschi M., Heidel F.H., Cavazzini F., Crugnola M., Bosi C., Isidori A., Auteri G., Forte D., Latagliata R., Griguolo D., Cattaneo D., Trawinska M., Bartoletti D., Krampera M., Semenzato G., Lemoli R.M., Cuneo A., Di Raimondo F., Vianelli N., Cavo M., and Palumbo G.A.
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Male ,Cancer Research ,Ruxolitinib ,ruxolitinib ,Gastroenterology ,0302 clinical medicine ,myelofibrosi ,80 and over ,risk factors ,blast phase ,myelofibrosis ,outcome ,Adult ,Aged ,Aged, 80 and over ,Blast Crisis ,Disease Progression ,Female ,Follow-Up Studies ,Humans ,Janus Kinases ,Middle Aged ,Primary Myelofibrosis ,Prognosis ,Pyrazoles ,Retrospective Studies ,Survival Rate ,Young Adult ,Incidence (epidemiology) ,Hematology ,General Medicine ,risk factor ,Oncology ,030220 oncology & carcinogenesis ,blast phase, myelofibrosis, outcome, risk factors, ruxolitinib, Blast Crisis, Disease Progression ,medicine.drug ,medicine.medical_specialty ,Socio-culturale ,Alpha interferon ,03 medical and health sciences ,Internal medicine ,Nitriles ,medicine ,Risk factor ,Myelofibrosis ,Survival rate ,business.industry ,Induction chemotherapy ,Anagrelide ,medicine.disease ,Pyrimidines ,business ,030215 immunology - Abstract
The impact of ruxolitinib therapy on evolution to blast phase (BP) in patients with myelofibrosis (MF) is still uncertain. In 589 MF patients treated with ruxolitinib, we investigated incidence and risk factors for BP and we described outcome according to disease characteristics and treatment strategy. After a median follow-up from ruxolitinib start of 3 years (range 0.1-7.6), 65 (11%) patients transformed to BP during (93.8%) or after treatment. BP incidence rate was 3.7 per 100 patient-years, comparably in primary and secondary MF (PMF/SMF) but significantly lower in intermediate-1 risk patients (2.3 vs 5.6 per 100 patient-years in intermediate-2/high-risk patients, P
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- 2020
38. Second primary malignancy in myelofibrosis patients treated with ruxolitinib
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Elena Maria Elli, Florian H. Heidel, Uros Markovic, Fabrizio Pane, Gianpietro Semenzato, Daniela Bartoletti, Francesca Palandri, Giulia Benevolo, Mauro Krampera, Malgorzata Monika Trawinska, Micaela Bergamaschi, Mario Tiribelli, Giovanni Caocci, Lucia Catani, Elisabetta Abruzzese, Massimo Breccia, Rossella Stella, Antonio Cuneo, Fabio D'Amore, Alessandro Isidori, Costanza Bosi, Monica Crugnola, Lisa Gandolfi, Domenico Russo, Alessandra Iurlo, Nicola Polverelli, Roberto M. Lemoli, Michele Cavo, Gianni Binotto, Roberto Latagliata, Francesco Cavazzini, Bruno Martino, Daniele Cattaneo, Nicola Vianelli, Novella Pugliese, Luigi Scaffidi, Massimiliano Bonifacio, Mariella D'Adda, Alessia Tieghi, Giuseppe Auteri, Giuseppe A. Palumbo, Polverelli N., Elli E.M., Abruzzese E., Palumbo G.A., Benevolo G., Tiribelli M., Bonifacio M., Tieghi A., Caocci G., D'Adda M., Bergamaschi M., Binotto G., Heidel F.H., Cavazzini F., Crugnola M., Pugliese N., Bosi C., Isidori A., Bartoletti D., Auteri G., Latagliata R., Gandolfi L., Martino B., Scaffidi L., Cattaneo D., D'Amore F., Trawinska M.M., Stella R., Markovic U., Catani L., Pane F., Cuneo A., Krampera M., Semenzato G., Lemoli R.M., Vianelli N., Breccia M., Russo D., Cavo M., Iurlo A., and Palandri F.
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Male ,Ruxolitinib ,Skin Neoplasms ,Lymphoma ,ruxolitinib ,Aggressive lymphoma ,Gastroenterology ,Hydroxycarbamide ,0302 clinical medicine ,myelofibrosi ,Risk Factors ,Neoplasms ,80 and over ,Aged, 80 and over ,Thrombocytosis ,Incidence (epidemiology) ,Incidence ,Hazard ratio ,Neoplasms, Second Primary ,Hematology ,Arteries ,Middle Aged ,Second Primary ,JAK inhibitor ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Context (language use) ,myelofibrosis ,JAK inhibitors ,second cancer ,toxicity ,NO ,03 medical and health sciences ,Internal medicine ,Nitriles ,medicine ,Humans ,Janus Kinase Inhibitors ,Myelofibrosis ,Aged ,Retrospective Studies ,business.industry ,Thrombosis ,medicine.disease ,Case-Control Studies ,Follow-Up Studies ,Multivariate Analysis ,Primary Myelofibrosis ,Pyrazoles ,Pyrimidines ,business ,030215 immunology - Abstract
Ruxolitinib (RUX), the first JAK1/JAK2 inhibitor approved for myelofibrosis (MF) therapy, has recently been associated with the occurrence of second primary malignancies (SPMs), mainly lymphomas and non-melanoma skin cancers (NMSCs). We analyzed the incidence, risk factors and outcome of SPMs in 700 MF patients treated with RUX in a real-world context. Median follow-up from starting RUX was 2·9years. Overall, 80 (11·4%) patients developed 87 SPMs after RUX start. NMSCs were the most common SPMs (50·6% of the cases). Multivariate analysis demonstrated that male sex [hazard ratio (HR): 2·37, 95% confidence interval (95%CI): 1·22–4·60, P=0·01] and thrombocytosis>400×109/l at RUX start (HR:1·98, 95%CI: 1·10–4·60, P=0·02) were associated with increased risk for SPMs. Risk factors for NMSC alone were male sex (HR: 3·14, 95%CI: 1·24–7·92, P=0·02) and duration of hydroxycarbamide and RUX therapy>5years (HR: 3·20, 95%CI: 1·17–8·75, P=0·02 and HR: 2·93, 95%CI: 1·39–6·17, P=0·005 respectively). In SPMs excluding NMSCs, male sex (HR: 2·41, 95%CI: 1·11–5·25, P=0·03), platelet>400×109/l (HR: 3·30, 95%CI: 1·67–6·50, P=0·001) and previous arterial thromboses (HR: 3·47, 95%CI: 1·48–8·14, P=0·004) were shown to be associated with higher risk of SPMs. While it is reassuring that no aggressive lymphoma was documented, active skin surveillance is recommended in all patients and particularly after prolonged hydroxycaramide therapy; oncological screening should be triggered by thrombocytosis and arterial thrombosis, particularly in males.
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- 2020
39. Biological significance and prognostic/predictive impact of complex karyotype in chronic lymphocytic leukemia
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Michele Laudisi, Francesco Cavazzini, Gian Matteo Rigolin, Antonio Urso, Luca Formigaro, Antonio Cuneo, Enrico Lista, Aurora Melandri, Antonella Bardi, Francesca Maria Quaglia, Melissa Dabusti, Elisa Tammiso, Elisa Menotti, Elena Saccenti, Massimo Negrini, Eleonora Volta, Maurizio Cavallari, Paolo Tomasi, and Maria Ciccone
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,complex karyotype ,Chronic lymphocytic leukemia ,Review ,NO ,03 medical and health sciences ,0302 clinical medicine ,Chemoimmunotherapy ,Internal medicine ,Complex Karyotype ,medicine ,Progression-free survival ,business.industry ,Mechanism (biology) ,Richter transformation ,chronic lymphocytic leukemia ,prognosis ,target therapy ,Karyotype ,medicine.disease ,Clinical trial ,030104 developmental biology ,030220 oncology & carcinogenesis ,Observational study ,business - Abstract
The complex karyotype (CK) is an established negative prognostic marker in a number of haematological malignancies. After the introduction of effective mitogens, a growing body of evidence has suggested that the presence of 3 or more aberrations by conventional banding analysis (CBA) is associated with an unfavorable outcome in chronic lymphocytic leukemia (CLL). Thus, the importance of CBA was recognized by the 2018 guidelines of the International Workshop on CLL, which proposed the introduction of CBA in clinical trials to validate the value of karyotype aberrations. Indeed, a number of observational studies showed that cytogenetic aberrations and, particularly, the CK may have a negative independent impact on objective outcome measures (i.e. time to first treatment, progression free survival, time to chemorefractoriness and overall survival) both in patients treated with chemoimmunotherapy and, possibly, in patients receiving novel mechanism-based treatment. Here, we set out to present the scientific evidence supporting the significance of CK as a prognostic marker in CLL and to discuss the biological basis showing that the CK is a consequence of genomic instability.
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- 2018
40. Choice of Frontline Tyrosine-Kinase Inhibitor in Very Elderly Patients with Chronic Myeloid Leukemia: A 'Campus CML' Study
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Sabina Russo, Paolo Sportoletti, Massimo Breccia, Jolanda Donatella Vincelli, Ambra Di Veroli, Mario Tiribelli, Rikard Mullai, Giuseppina Loglisci, Pamela Murgano, Anna Rita Scortechini, Debora Luzi, Monica Bocchia, Sabrina Leonetti Crescenzi, Cristina Bucelli, Fabio Stagno, Alessandro Maggi, Federica Sorà, Mario Annunziata, Massimiliano Bonifacio, Elisabetta Abruzzese, Alessandra Malato, Isabella Capodanno, Annapaola Leporace, Giovanni Caocci, Roberto Latagliata, Giuseppe Saglio, Imma Attolico, Francesco Cavazzini, Luigiana Luciano, Giorgina Specchia, Elena Crisà, Gianni Binotto, Rosaria Sancetta, Chiara Elena, Carmen Fava, Alessandra Iurlo, Maria Cristina Miggiano, Gioia Colafigli, Monica Crugnola, and Davide Rapezzi
- Subjects
business.industry ,medicine.drug_class ,Immunology ,Cancer research ,Medicine ,Myeloid leukemia ,Cell Biology ,Hematology ,business ,Biochemistry ,Tyrosine-kinase inhibitor - Abstract
Introduction Treatment of chronic phase (CP) chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs) proved to be almost equally effective in young and elderly patients. Three TKIs, imatinib (IM), dasatinib (DAS) and nilotinib (NIL), are approved for frontline therapy in Italy. Choice of frontline TKI is based on a combined evaluation of patient's characteristics and expectations, with age usually playing a prominent role. However, to date, few data are available on patterns of TKI selection in very elderly patients. Aim To analyse the use of frontline TKI therapy in a large and unselected cohort of very elderly CP-CML patients Methods We retrospectively evaluated 332 patients aged ≥75 year diagnosed from 1/2012 to 12/2019 at 36 Hematology Centres participating at the "Campus CML" project. Results Clinical features at diagnosis for the whole cohort and according to frontline TKI are reported in Table 1. As to frontline TKI, 285 patients (85.8%) received IM and 47 (14.2%) a 2G-TKI (DAS n=28, 59.5%; NIL n=19, 40.5%). Of the 285 IM-treated patients, 192 (67.3%) started with standard dose (400 mg/day) and 93 (32.7%) with a reduced dose (300 mg/day n=64, 22.5%; Following widespread introduction of generic IM in Italy in early 2018, patients were divided in 2 groups: among 238 patients diagnosed from 2012 to 2017, 198 (83.1%) received IM and 40 (16.9%) a 2G-TKI, while patients diagnosed in 2018-2019 were treated with IM in 87/94 (92.5%) cases and with a 2G-TKI in 7 (7.5%) cases only (p=0.028). Conclusions IM remains the frontline drug of choice in very elderly CML patients, and this trend seems to increase after the introduction of the generic formulation. However, 2G-TKI are used in a small but sizeable group of patients, without a clear correlation with baseline CML features, thus probably reflecting a physician's evaluation of patient's fitness and/or expectation. Efficacy and safety of initial reduced TKIs doses in the setting of very elderly patients warrant further analyses. Figure 1 Figure 1. Disclosures Latagliata: Novartis: Honoraria; BMS Cellgene: Honoraria; Pfizer: Honoraria. Bonifacio: Novartis: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Bristol Myers Squibb: Honoraria. Elena: CELGENE: Other: funding for meeting participation; PFIZER: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; GILEAD: Membership on an entity's Board of Directors or advisory committees. Iurlo: Novartis: Speakers Bureau; Incyte: Speakers Bureau; Pfizer: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Stagno: Pfizer: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; InCyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Support for attending meetings and/or travel, Research Funding. Abruzzese: Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Breccia: Bristol Myers Squibb/Celgene: Honoraria; Incyte: Honoraria; Abbvie: Honoraria; Pfizer: Honoraria; Novartis: Honoraria.
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- 2021
41. Analysis of Early Events during the First Year of Tyrosine Kinase Inhibitor Therapy in Patients with Chronic Phase - Chronic Myeloid Leukemia: A 'Campus CML' Study
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Sabrina Leonetti Crescenzi, Elena Crisà, Isabella Capodanno, Carmen Fava, Immacolata Attolico, Gianni Binotto, Debora Luzi, Maria Cristina Miggiano, Andrea Bernardelli, Massimiliano Bonifacio, Maria Basile, Giuseppina Loglisci, Chiara Elena, Fabio Stagno, Anna Rita Scortechini, Olga Mulas, Cristina Bucelli, Roberto Latagliata, Alessandra Malato, Francesco Cavazzini, Giovanni Caocci, Luigiana Luciano, Giuseppe Saglio, Ambra Di Veroli, Paolo Sportoletti, Giorgina Specchia, Monica Bocchia, Umberto Pizzano, Massimo Breccia, Michele Pizzuti, Annapaola Leporace, Emilia Scalzulli, Malgorzata Monika Trawinska, Mario Tiribelli, Sabina Russo, Pamela Murgano, Monica Crugnola, Davide Rapezzi, and Alessandra Iurlo
- Subjects
business.industry ,medicine.drug_class ,Immunology ,Cancer research ,Medicine ,In patient ,Cell Biology ,Hematology ,Chronic phase chronic myeloid leukemia ,business ,Biochemistry ,Tyrosine-kinase inhibitor - Abstract
Background Tyrosine kinase inhibitors (TKIs) revolutionized treatment of chronic myeloid leukemia (CML). However, the first months of therapy are crucial, as optimal response is defined as the achievement of molecular milestones at 3, 6 and 12 months (mo.) and as many toxicities, also causing a TKI switch, are more frequent in the 1st year. Methods To evaluate achievement of early molecular response (MR) and incidence of events leading to a TKI change during the 1st year of therapy, we retrospectively studied 1650 CP-CML patients diagnosed from 2012 and 2019 at 31 Hematology Centres and treated with frontline imatinib (IM) or second-generation (2G) TKIs dasatinib or nilotinib. Optimal MR at 3, 6 and 12 mo. were assessed according to 2020 ELN recommendations. Results Frontline TKI was IM in 926 (56.1%) and 2G-TKIs in 724 (43.9%) cases: the main clinical features at diagnosis of the entire cohort and according to frontline treatment is reported in the Table 1. Commonest comorbidities were arterial hypertension (38.7%), previous neoplasm (13.6%), diabetes (11.3%), peripheral vascular diseases (7.8%), COPD (7.5%) and ischemic heart disease (6.8%). IM-treated patients were older (p Optimal MR was achieved at 3 mo. by 1186/1430 (82.9%), at 6 mo. by 1025/1352 (75.8%) and at 12 mo. by 826/1264 patients (65.3%), respectively. Total number of patients discontinuing TKI in the 1st year was 321/1650 (19.4%), being higher with IM (237/926, 25.5%) than 2G-TKIs (84/724, 11.6%) (p0.001), hematologic toxicity (1.7%, 2.0% IM vs 1.4% 2G-TKIs, p=0.25) and progression (1.0%, 1.2% IM vs 0.8% 2G-TKIs, p=0.56). Cumulative incidence of discontinuation at 3, 6 and 12 mo. were 5.6%, 10.7% and 19.3%, respectively; values for IM and 2G-TKIs at the three timepoints were 8.1%, 15.0%, 25.5% and 2.5%, 5.3%, 11.5% (p Conclusions This real-world study on over 1600 CML patients shows that almost 20% discontinue frontline TKI during the 1st year, mostly for primary resistance or toxicity. Discontinuation rates are higher with IM compared to 2G-TKIs, mostly at 3 mo. and are probably due to a lower attainment of early MR. The impact of older age, higher risks and heavier burden of comorbidities in IM patients should be considered and need deeper investigation. Figure 1 Figure 1. Disclosures Elena: GILEAD: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; PFIZER: Membership on an entity's Board of Directors or advisory committees; CELGENE: Other: funding for meeting participation. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Stagno: InCyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Novartis: Consultancy, Honoraria, Other: Support for attending meetings and/or travel, Research Funding. Iurlo: Pfizer: Speakers Bureau; Incyte: Speakers Bureau; Novartis: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Bonifacio: Novartis: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Bristol Myers Squibb: Honoraria. Breccia: Pfizer: Honoraria; Incyte: Honoraria; Abbvie: Honoraria; Bristol Myers Squibb/Celgene: Honoraria; Novartis: Honoraria. Latagliata: Novartis: Honoraria; Pfizer: Honoraria; BMS Cellgene: Honoraria.
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- 2021
42. Efficacy and Safety of Ruxolitinib in the Treatment of Elderly Patients with Policythemia Vera Resistant/Intolerant to Hydroxyurea
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Massimiliano Bonifacio, Elena Maria Elli, Giuseppe Auteri, Giovanni Caocci, Daniela Bartoletti, Francesco Mendicino, Roberto Latagliata, Giulia Benevolo, Francesco Cavazzini, Novella Pugliese, Mario Tiribelli, Elena Rossi, Massimo Breccia, Monica Crugnola, Valerio De Stefano, Bruno Martino, Ambra Di Veroli, Francesca Palandri, Nicola Vianelli, Alessandro Andriani, Alessandra D'Addio, Florian H. Heidel, Giuseppe A. Palumbo, Michele Cavo, Alessia Tieghi, and Gianni Binotto
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Oncology ,Ruxolitinib ,medicine.medical_specialty ,business.industry ,Internal medicine ,Immunology ,medicine ,Cell Biology ,Hematology ,business ,Biochemistry ,medicine.drug - Abstract
Introduction: Ruxolitinib (Rux) has been recently approved as second-line therapy in patients (pts) with Polycythemia Vera (PV) resistant/intolerant to hydroxyurea (HU). Median age of PV pts enrolled in the pivotal Response trials was around 60 yrs; at present, no data is reported on the use of Rux in elderly pts. Aims: In a real-world cohort of PV pts treated with Rux, we investigated whether the efficacy and safety of Rux were comparable in pts who initiated therapy when aged ≥75 years compared with younger pts. Methods: After IRB approval, clinical/laboratory data of 934 WHO2016-defined PV pts followed in 29 Hematology Centers were retrospectively collected. Of them, 168 (17.9%) were considered resistant/intolerant to HU at any time during follow-up by responsible physician and shifted to Rux as second-line therapy. Results: Among the 168 pts treated with Rux, 42 (25%, median age 78.2 years) were aged ≥75 yrs at Rux start, 74 (44%, median age 67.7) were aged 60-74 and 52 (31%, median age 53) were No significant differences were observed between the 3 groups, apart from a lower need for phlebotomies in pts aged ≥75 yrs and lower presence of palpable spleen in older pts (age ≥60), that more frequently switched to Rux due to HU intolerance (Table 1). Median duration of HU treatment was 41.0 months (IQR 14.6 - 85.8), with a trend for a longer median treatment duration in pts aged ≥75 [61.0 months (IQR 21.5 - 89.6) vs 35.9 months (IQR 13.4 - 79.6), p=0.04]. Rux starting dose was similar across age groups; however, more elderly pts underwent Rux dose reductions during follow-up (45.2% in pts aged ≥75 vs 28.6% in younger pts, p=0.04). Responses during Rux therapy are reported in Table 2, with no significant differences between the 3 groups at any time. In the overall cohort, response on PV-related symptoms at 6 and 12 months was significantly higher in pts who switched to Rux because of HU intolerance; however, this difference was not observed in pts aged ≥75 yrs. As to the most common hematologic Rux-related toxicities, grade 3-4 anemia and thrombocytopenia were observed in only 2 (1.2%) and 5 (3%) pts, with no difference across age groups (p=0.45 and p=0.18). However, any grade anemia and thrombocytopenia during Rux were more frequently observed in pts aged ≥75 (68.3% vs 51.7% of anemia, p=0.06 and 12.2% vs 3.5% of thrombocytopenia in younger pts, p=0.04). Nineteen and 4 pts experienced infectious and thrombotic complications during Rux with incidence rates of 0.59 and 0.12 per 100 patient-months, respectively, comparably in younger and older (≥75) pts (p=0.75 and p=0.29, respectively). Notably, 6 infections were herpes simplex/zoster virus, comparably distributed between the 3 groups (p=0.60). Permanent Rux discontinuation was needed in 14 pts (8.3%) after a median Rux exposure of 7.8 months (IQR 4.6 - 17.6) (incidence: 0.41 per 100 pts/months). Discontinuation was comparable between age groups, with Rux stop in 4 pts aged ≥75 yrs and 10 younger pts (2.4% vs 5.2% at 8 months, log-rank p=0.75). At last follow-up, 2 pts had died (1 from 2 nd neoplasia after 19.1 months from Rux start and 1 from acute leukemia after 3.3 years), both pts aged 60-74 yrs. Conclusions. In this real-world analysis, use of Rux in HU resistant/intolerant elderly PV pts was effective and safe despite the more frequent need for dose reductions. Older age should not discourage Rux therapy, but stricter hematological monitoring may be suggested. Figure 1 Figure 1. Disclosures Latagliata: BMS Cellgene: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Breccia: Pfizer: Honoraria; Incyte: Honoraria; Bristol Myers Squibb/Celgene: Honoraria; Abbvie: Honoraria; Novartis: Honoraria. Bonifacio: Amgen: Honoraria; Bristol Myers Squibb: Honoraria; Novartis: Honoraria; Pfizer: Honoraria. Cavo: Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Palandri: AOP: Membership on an entity's Board of Directors or advisory committees; Sierra Oncology: Membership on an entity's Board of Directors or advisory committees; CTI: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.
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- 2021
43. Peripheral Blasts Are Associated with Response to Ruxolitinib and Outcome in Patients with Chronic-Phase Myelofibrosis
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Bruno Martino, Eloise Beggiato, Mario Tiribelli, Francesco Cavazzini, Novella Pugliese, Giovanni Caocci, Antonio Cuneo, Monica Crugnola, Emanuela Ottaviani, Massimo Breccia, Mauro Krampera, Daniela Bartoletti, Carmen Fava, Giorgia Micucci, Elisabetta Abruzzese, Michele Cavo, Gianni Binotto, Nicola Polverelli, Fabrizio Pane, Giulia Benevolo, Christian Di Pietro, Monica Bocchia, Massimiliano Bonifacio, Daniela Cilloni, Roberto M. Lemoli, Florian H. Heidel, Francesca Palandri, Giuseppe A. Palumbo, Malgorzata Monika Trawinska, Alessandra Iurlo, Elena Maria Elli, Alessia Tieghi, Giuseppe Auteri, Nicola Vianelli, Maurizio Miglino, and Costanza Bosi
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Oncology ,medicine.medical_specialty ,Ruxolitinib ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Outcome (game theory) ,Peripheral ,Internal medicine ,medicine ,In patient ,Myelofibrosis ,business ,medicine.drug - Abstract
Background: The presence of peripheral blasts (PB) is a negative prognostic factor in patients (pts) with primary and secondary myelofibrosis (PMF/SMF) and PB ≥4% was associated with a particularly unfavorable prognosis (Masarova L et al, Cancer 2020). Ruxolitinib (RUX) is the JAK1/2 inhibitor most used for treatment of MF-related splenomegaly and symptoms. Its role has not been assessed in correlation with PB. Aims: To evaluate the impact of PB percentage on RUX efficacy and prognosis Methods: After IRB approval, the "RUX-MF" retrospective study collected 804 RUX-treated chronic-phase (CP, defined as PB Comparisons of quantitative variables between the 3 groups were carried out by Kruskal-Wallis and Dunn's tests while association between categorical variables was tested by the χ2 test. Variables significantly associated to RUX stop/leukemic transformation (LT)/overall survival (OS) in univariate analysis (Log-rank test) were considered for multivariable analyses, carried out using the Cox regression model, with evaluation of the model's performance in terms of goodness of fit. Results: Pts were categorized according to PB at RUX start: PB-0 (no PB; n. 487, 61.3%), PB-5 (PB 1-5%; n. 283, 35.8%), and PB-9 (PB 6-9%; n. 24, 2.9%). Pts characteristics at RUX start were: median age 68.1y (24-89); males 58.1%; PMF 52.5%; JAK2, CALR and MPL mutated: 80.5%, 13.1% and 2% (4.4% triple negative), high DIPSS: 7.6%; PLT25 x10 9/l: 10.8%/16.4%; spleen length ≥10 cm: 47.8%, TSS ≥20: 60.6%; ≥1/≥2 high-risk mutation (HMR): 69/18 out of 167 evaluable (41.3%/10.8%); fibrosis grade ≥2: 77.9%; starting/cumulative RUX dose ≥15 mg BID: 61.4%/52.6%. Higher PB count was associated to high DIPSS risk (PB-0: 1.9%, PB-5: 16.2%, PB-9: 21.7%, p At 3 and 6 mos, 26.9% and 30.4% of evaluable pts achieved a SR, while 59.7% and 68.1% were in SyR, respectively. At 3 mos, SR (PB-0: 31.8%, PB-5: 20.6%, PB-9: 10%, p=0.001) and SyR (PB-0: 62.9%, PB-5: 55.5%, PB-9: 36.8%, p=0.02) were less frequently achieved by PB-5 and PB-9 pts compared to PB-0 pts. This association remained significant for SR at 6 mos (PB-0: 35%, PB-5: 23.9%, PB-9: 14.3%, p=0.006) and for both SR (p=0.003) and SyR (p=0.01) at any time. After a median RUX exposure of 1.5 y (0.1-8.9), 491 (61.8%) pts stopped RUX, 110 (13.9%) had a LT and 365 (46%) died. In univariate analysis, at 2y PB-9 pts had higher rates of RUX stop (73.9% vs 40.8% and 34.3% in PB-5 and PB-0 pts, log-rank p In multivariable analysis, PB-9 pts confirmed their association with: 1) RUX stop (HR 3.74, 95%CI 1.51-3.70, p20 (HR 1.66, 95%CI 1.05-2.61, p=0.03), and HMR≥2 (HR 2.69, 95%CI 1.26-4.47, p=0.007); 2) LT (HR 3.71, 95%CI 1.71-8.04, p Conclusions: CP-MF pts with PB>5% have a worse response to RUX and a worse outcome. Personalized approaches beyond RUX monotherapy may be useful in this context. Further clinical trials evaluating combination strategies and new drugs are required. Figure 1 Figure 1. Disclosures Palandri: Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; AOP: Membership on an entity's Board of Directors or advisory committees; Sierra Oncology: Membership on an entity's Board of Directors or advisory committees; CTI: Consultancy. Abruzzese: Bristol Myers Squibb: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Iurlo: Bristol Myers Squibb: Speakers Bureau; Pfizer: Speakers Bureau; Novartis: Speakers Bureau; Incyte: Speakers Bureau. Bonifacio: Bristol Myers Squibb: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Amgen: Honoraria. Cuneo: AbbVie: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau. Pane: AbbVie; Amgen; Novartis: Other: Travel, accommodation, expenses; Novartis Pharma SAS;: Research Funding; AbbVie; Amgen; Novartis, GSK , Incyte: Consultancy; AbbVie; Amgen; Novartis, GSK, Incyte: Speakers Bureau. Lemoli: Celgene: Other: Support for attending meetings and/or travel; Jazz, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie, Daiichi Sankyo, Servier: Honoraria, Speakers Bureau. Cavo: Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Adaptive Biotechnologies: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Breccia: Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; Bristol Myers Squibb/Celgene: Honoraria; Abbvie: Honoraria.
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- 2021
44. Durability of spleen response affects the outcome of ruxolitinib-treated patients with myelofibrosis: Results from a multicentre study on 284 patients
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Giuseppe Auteri, Nicola Sgherza, Mario Tiribelli, Lucia Catani, Daniela Bartoletti, Costanza Bosi, Roberto Latagliata, Francesco Cavazzini, Michele Cavo, Franco Aversa, Bruno Martino, Massimiliano Bonifacio, Antonio Cuneo, Gianni Binotto, Giuseppe A. Palumbo, Massimo Breccia, Adalberto Ibatici, Nicola Vianelli, Alessandro Isidori, Monica Crugnola, Gianpietro Semenzato, Alessia Tieghi, Micaela Bergamaschi, Maura Nicolosi, Francesca Palandri, Alessandra Iurlo, Nicola Polverelli, Elisabetta Abruzzese, Giulia Benevolo, Florian H. Heidel, Palandri, Francesca, Palumbo, Giuseppe A, Bonifacio, Massimiliano, Breccia, Massimo, Latagliata, Roberto, Martino, Bruno, Polverelli, Nicola, Abruzzese, Elisabetta, Tiribelli, Mario, Nicolosi, Maura, Bergamaschi, Micaela, Tieghi, Alessia, Iurlo, Alessandra, Sgherza, Nicola, Cavazzini, Francesco, Isidori, Alessandro, Binotto, Gianni, Ibatici, Adalberto, Crugnola, Monica, Heidel, Florian, Bosi, Costanza, Bartoletti, Daniela, Auteri, Giuseppe, Catani, Lucia, Cuneo, Antonio, Aversa, Franco, Semenzato, Gianpietro, Cavo, Michele, Vianelli, Nicola, and Benevolo, Giulia
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Male ,Oncology ,Cancer Research ,Ruxolitinib ,medicine.medical_specialty ,Time Factors ,ruxolitinib,myelofibrosis, spleen ,Socio-culturale ,Spleen ,03 medical and health sciences ,0302 clinical medicine ,Hematology ,Internal medicine ,80 and over ,medicine ,Humans ,Myelofibrosis ,Aged ,business.industry ,Aged, 80 and over ,Female ,Middle Aged ,Organ Size ,Rituximab ,Primary Myelofibrosis ,medicine.disease ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,business ,030215 immunology ,medicine.drug - Abstract
NA
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- 2018
45. Differential Treatment Strategy in Polycythemia Vera Patients with Stable Suboptimal Response to Hydroxyurea: Clinical Correlations and Impact on Survival
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Enrica Antonia Martino, Antonio Cuneo, Fabrizio Pane, Luigi Scaffidi, Giuseppe Auteri, Michele Cavo, Bruno Martino, Roberto Latagliata, Alessia Tieghi, Francesco Cavazzini, Gianpietro Semenzato, Rossella Stella, Monica Crugnola, Francesco Mendicino, Novella Pugliese, Nicola Polverelli, Mauro Krampera, Roberto M. Lemoli, Massimiliano Bonifacio, Daniela Bartoletti, Giuseppe A. Palumbo, Mario Tiribelli, Nicola Vianelli, Lucia Catani, Elena Maria Elli, Alessandra D'Addio, Gianni Binotto, Francesca Palandri, Fabio D'Amore, Massimo Breccia, Simona Tomassetti, Florian H. Heidel, Giovanni Caocci, and Giulia Benevolo
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medicine.medical_specialty ,Polycythemia vera ,Differential treatment ,business.industry ,Internal medicine ,Immunology ,Medicine ,Cell Biology ,Hematology ,business ,medicine.disease ,Biochemistry ,Gastroenterology - Abstract
Introduction: Hydroxyurea (HU) is the most used cytoreductive therapy (tx) for patients (pts) with polycythemia vera (PV). However, many pts may have suboptimal responses (SubOR) and/or toxicity (TOX) to HU. After HU, Ruxolitinib (RUX) may achieve hematocrit (HCT) and spleen reductions, but other tx are also available, mainly busulfan (BUS) and interferons (IFN). Aims: In a large cohort of PV pts, we investigated if: 1) type of SubOR to HU influenced subsequent tx strategy; 2) differential tx had an impact on overall survival (OS). Methods: After IRB approval, clinical/laboratory data of 2016 WHO-defined PV pts from 21 European Hematology Centers were retrospectively collected. SubOR included ≥1 of the following criteria after ≥3 mos of HU: WBC/PLT count >10/400 x109/l, need for phlebotomies (PHL); splenomegaly and/or symptoms persistence/occurrence (Barosi G et al, Blood 2009). Only pts with stable SubOR were included in this analysis. Since a complete response was never achieved, the index date (ID) was set at 3 mos from HU start in all pts (Barosi G et al, BJH 2009). OS was calculated from the ID by Cox analysis with age>80, adjusted with left truncation from PV diagnosis. Results: At data cut-off date (June 2020), 808 PV pts were collected; 688 received HU. Among the 452 (65.7%) pts who presented a stable SubOR to HU, 41 did not receive any tx for PV due to early death or progression to BP/MF and were excluded from this analysis. Baseline characteristics of the 411 evaluable pts were: median age: 65 yrs (21- 87); males: 54%; median (range) WBC/PLT count, x109/l: 10 (1.1-38)/465 (139-1209); median Hb (g/dl)/HCT (%): 18.6/56 (males); 17.6/54 (females); palpable splenomegaly: 38%; symptoms: 80.5%; pruritus: 42%. A previous thrombosis occurred in 104 (25.3%) pts. At least one cardiovascular risk factor (CVRF: smoke, diabetes, hypertension, dyslipidemia and overweight) was present in 325 pts (79.1%). After a median follow-up of 4.8 yrs (0.5-27.6) from HU start, 104 (25.3%) switched to RUX (HU-RUX), 18 (4.4%) switched to another agent (HU-other, including IFN, BUS, PHL only), and 289 (70.3%) continued HU (HU-alone). Pts with baseline palpable spleen (p While 331 (80.5%) pts had a stable SubOR without TOX, 80 (19.5%) had also TOX. Notably, pts with only SubOR more frequently continued HU (p In 45.5% of pts, the SubOR was related only to uncontrolled WBC/PLT/HCT, while 16.1% of pts had an optimal hematological control but presented spleen/symptoms; the remaining 38.4% of pts had both uncontrolled myeloproliferation and spleen/symptoms. The presence of both uncontrolled myeloproliferation and spleen/symptoms significantly predicted RUX switch (p Investigating the SubOR criteria individually among the HU-alone/other and the HU-RUX groups, we found that uncontrolled leukocytosis and/or thrombocytosis (p After the ID, 31 pts died. HU-RUX pts presented increased OS compared to HU-alone/other pts (p=0.03). Conclusions. This study revealed a high rate of SubOR to HU, possibly also affected by low HU doses, and a lack of urgency to change the tx in these pts, with >70% of pts continuing HU despite the stable SubOR. Particularly, good tolerance to HU, absence of splenomegaly and pruritus, and older age were the main factors against a tx change. Notably, despite HCT>45% is associated with worse outcome (Marchioli R, NEJM 2013), PHL need did not significantly trigger tx change. The better OS in the HU-RUX group is presumably multifactorial and requires further confirmation. Overall, this analysis points out the need to improve HU management and response evaluations, weighing appropriate tx strategies in case of SubOR. Disclosures Palandri: Novartis: Consultancy, Honoraria. Benevolo:Amgen: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Breccia:Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Abbvie: Consultancy; Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Cavazzini:Pfize: Honoraria; Novartis: Honoraria; Incyte: Honoraria. Heidel:Celgene: Consultancy; CTI: Consultancy; Novartis: Consultancy, Research Funding. Crugnola:BMS: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Pane:Daiichi Sankyo: Consultancy, Other: Travel Expenses; Janssen: Other: Travel Expenses; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Other: travel expenses, Speakers Bureau; Novartis pharma SAS: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Other: Travel Expenses, Speakers Bureau; AbbVie: Consultancy, Other: Travel Expenses, Speakers Bureau. Cuneo:Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra Zeneca: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Krampera:Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Semenzato:Takeda: Honoraria; Roche: Honoraria; Abbvie: Honoraria. Lemoli:Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; BerGenBio ASA: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Palumbo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
- Published
- 2020
46. Ruxolitinib Rechallenge in Resistant/Intolerant MF Patients: Frequency, Therapeutic Effects, and Impact on Outcome
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Antonio Cuneo, Giulia Benevolo, Giuseppe A. Palumbo, Massimiliano Bonifacio, Mario Tiribelli, Giuseppe Auteri, Massimo Breccia, Lucia Catani, Monica Crugnola, Giovanni Caocci, Luigi Scaffidi, Daniela Bartoletti, Michele Cavo, Francesca Palandri, Nicola Polverelli, Roberto M. Lemoli, Elena Maria Elli, Elena Masselli, Bruno Martino, Daniele Cattaneo, Florian H. Heidel, Gianni Binotto, Alessandra Iurlo, Fabrizio Pane, Mauro Krampera, Costanza Bosi, Nicola Vianelli, Roberto Latagliata, Francesco Cavazzini, Novella Pugliese, Rossella Stella, Giorgia Micucci, Gianpietro Semenzato, and Alessia Tieghi
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Ruxolitinib ,Disease status ,medicine.medical_specialty ,business.industry ,INVESTIGATIONAL AGENTS ,Immunology ,Therapeutic effect ,Context (language use) ,Cell Biology ,Hematology ,Biochemistry ,Symptoms score ,Discontinuation ,Internal medicine ,Medicine ,business ,Bristol-Myers ,medicine.drug - Abstract
Introduction: The outcome of patients (pts) with myelofibrosis (MF) who discontinue ruxolitinib (RUX) is poor with scarce therapeutic possibilities (Palandri et al, 2020). However, some evidences suggest that pts may respond to a rechallenge of RUX after drug stop (Gerds et al, 2018). Aims: To investigate in a real-world context: 1) frequency and reasons for rechallenge; 2) therapeutic effects of rechallenge; 3) impact of rechallenge on overall survival (OS) Methods: After IRB approval, a clinical database was created in 20 European Hematology Centers including now retrospective data of 703 MF pts who started RUX from Jan 2011 to Nov 2019. Only chronic phase (CP) pts who stopped RUX for ≥14 days and survived ≥30 days after discontinuation were included. A specific survey collected clinical/laboratory data at RUX stop and at rechallenge, reasons for discontinuation and treatments before rechallenge. OS was estimated from the date of the first/only RUX discontinuation to last contact (log-rank test). Results: A total of 219 CP pts was evaluable for this study. In 60 (27.4%) pts, RUX was re-challenged for ≥14 days after the first discontinuation (RUX-again), while 159 (72.6%) pts discontinued RUX permanently (RUX-stop). The median time from RUX start to stop was of 16.5 and 12.3 mos for RUX-again and RUX-stop pts, respectively (p=0.41). At RUX start, characteristics of RUX-again were: median age 67y (24-88); males 61.7%; PMF 53.3%; median Hb 10.2 g/dl; median PLT/WBC: 249/12.6 x109/l; median RUX starting dose: 15mg BID. Baseline characteristics of RUX-again and RUX-stop pts were comparable. In the 60 RUX-again pts, reasons for discontinuation included loss of/inadequate response (18 pts, 30%) and toxicity (42 pts, 70%). Toxicity included G3-4 thrombocytopenia (38.1%), anemia (26.2%), infections (21.4%), other (14.3%). Conversely, RUX-stop pts discontinued RUX mainly due to loss of/inadequate response (75 pts, 47.2%), while intolerable toxicity occurred in 69 pts (43.4%) (p=0.004) and other causes in 9.4%. At first RUX discontinuation, 35.7% of RUX-again pts presented with large (>10 cm) splenomegaly; median Total Symptoms Score (TSS) was 10 (TSS>20 in 30.4% of pts). The median duration of temporary RUX discontinuation was 2 mos (range 0.5-71.1). During RUX stop, 65% of RUX-again pts did not receive any therapy, 15% received only palliation (steroids, hydroxyurea), while 11.7% switched to investigational agents, 3.3% underwent splenectomy and 5% allogeneic transplantation. Compared to disease status at first RUX stop, at RUX restart there was a significant increase of pts with large splenomegaly and high TSS, while the PLT count was higher and RUX dose significantly lower (Table 1). The median duration of RUX rechallenge was 7.5 mos (0.5-72.7). During the rechallenge, 44.6% and 48.3% pts improved spleen and symptoms, and there was a significant increase in pts with TSS reduction (p=0.01); 8 pts (13.3%) continued RUX with stable/worsening spleen size and improvement in TSS. Conversely, 26.8% and 20% of pts had increase in spleen size and in symptoms, respectively. While Hb levels remained stable, PLT count significantly decreased during rechallenge (p The reasons for temporary discontinuation had no impact on the reduction of spleen/symptoms during rechallenge and on OS. However, comparing RUX-again and RUX-stop pts, RUX-again pts showed a better OS, with a median survival of 41.1 mos and 23.7, respectively in the 2 cohorts (Fig. 1). Conclusions: This real-world study highlights that RUX rechallenge is quite common in CP-MF pts, involving almost 30% of treated pts, particularly when the discontinuation is due to toxicity. The temporary discontinuation, while improving PLT count, generally caused a significant increase in disease burden. After rechallenge, almost 50% of pts achieved clinical responses regardless of reason of first discontinuation. This residual disease control activity, that correlated with improved OS, should be weighed up also given the new therapeutic possibilities available in these pts. Disclosures Palandri: Novartis: Consultancy, Honoraria. Breccia:Abbvie: Consultancy; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Benevolo:Amgen: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Cavazzini:Incyte: Honoraria; Pfize: Honoraria; Novartis: Honoraria. Crugnola:Janssen: Honoraria; BMS: Honoraria; Novartis: Honoraria; Celgene: Honoraria. Heidel:CTI: Consultancy; Celgene: Consultancy; Novartis: Consultancy, Research Funding. Pane:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Other: travel expenses, Speakers Bureau; Daiichi Sankyo: Consultancy, Other: Travel Expenses; Novartis pharma SAS: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Other: Travel Expenses; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Other: Travel Expenses, Speakers Bureau; AbbVie: Consultancy, Other: Travel Expenses, Speakers Bureau. Cuneo:janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Krampera:Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Semenzato:Takeda: Honoraria; Roche: Honoraria; Abbvie: Honoraria. Lemoli:AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; BerGenBio ASA: Research Funding. Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Palumbo:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
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- 2020
47. First Line Treatment with Hydroxyurea in Patients with Policitemia Vera: Evaluation of Efficacy in the Current Clinical Practice Beyond ELN Criteria
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Francesco Mendicino, Massimo Breccia, Mauro Krampera, Mario Tiribelli, Lucia Catani, Bruno Martino, Massimiliano Bonifacio, Alessandra D'Addio, Alessia Tieghi, Daniela Bartoletti, Gianni Binotto, Ambra Di Veroli, Enrica Antonia Martino, Florian H. Heidel, Elena Maria Elli, Giovanni Caocci, Gianpietro Semenzato, Michele Cavo, Fabrizio Pane, Roberto Latagliata, Simona Tomassetti, Francesco Cavazzini, Giuseppe A. Palumbo, Giulia Benevolo, Novella Pugliese, Luigi Scaffidi, Antonio Cuneo, Francesca Palandri, Fabio D'Amore, Nicola Polverelli, Monica Crugnola, Roberto M. Lemoli, Rossella Stella, Nicola Vianelli, and Giuseppe Auteri
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First line treatment ,Clinical Practice ,medicine.medical_specialty ,business.industry ,Immunology ,Medicine ,In patient ,Cell Biology ,Hematology ,Current (fluid) ,business ,Intensive care medicine ,Biochemistry - Abstract
Introduction Hydroxyurea (HU) is worldwide used in the current clinical practice as first line treatment in high risk patients with Polycythemia Vera (PV). However, its efficacy has been seldom evaluated in the real-life setting. Aims The present study aims to address the role of Complete Peripheral Recovery (CPR) as useful response criteria in PV patients treated with HU in a large cohort of unselected patients. Methods After IRB approval, data of 846 PV patients, revised according to WHO2008/2016 and followed in 21 European Hematology Centers, were retrospectively collected. Definition of CPR during HU treatment included all the following criteria: hematocrit (Ht) level ≤45% (≤3 phlebotomies per year allowed), white blood cells (WBC) count ≤10 x109/l, platelets (PLT) count ≤ 400 x109/l. Spleen size and symptoms were not considered in the definition of CPR. Event-free survival (EFS), considering as event evolution into blast phase (BP) or myelofibrosis (MF) and death from any cause, was calculated from HU start to last contact/event by Cox analysis with age≥70y. Overall survival (OS) was calculated from the start of HU to last contact/death (log-rank p). Results Among the 846 patients of the entire cohort, 724 (85.5%) were treated with HU after a median time from PV diagnosis of 2.6 months [interquartile range (IQR) 0.5 - 19.6]: the main clinical features of these 724 patients at diagnosis are reported in the Table 1. Starting doses of HU, available in 709 patients, were 1000 mg/day in 38 (5.4%). Twenty-five patients were not evaluable for response to HU. Among the remaining 699 patients, 426 (60.9%) achieved a CPR after a median time from HU start of 4.9 months (IQR 2.1 - 15.7) while 273 (39.1%) never achieved a CPR. Among the 426 patients who achieved CPR, 115 (26.9%) needed a treatment period >12 months before obtaining the CPR. The main baseline clinical features of patients achieving or not CPR are reported in the Table 1: female sex, older age at diagnosis and at HU start, lower WBC count, no phlebotomies need and no palpable spleen were all associated in univariate analysis with CPR achievement. During HU treatment, a thrombotic episode occurred in 36 patients achieving CPR (8.4%) compared to 16 patients without CPR (5.8%) (p=0.162). Among 426 patients achieving CPR, 20 (4.6%) evolved in MF and 10 (2.3%) evolved in BP: among 273 patients without CPR, 20 (7.3%) evolved in MF and 9 (3.3%) evolved in BF (p=0.134 and 0.451, respectively). Ten-year EFS was 79.2% [95%Confidence Interval (CI) 72.1 - 84.8] in patients achieving CPR compared to 67.3% (95%CI 56.9 - 75.7) in patients without CPR (p=0.001) (Fig. 1). Ten-year OS was 80.5% (95%CI 73.9 - 87.1) in patients achieving CPR compared to 74.4% (95%CI 65.6 - 83.2) in patients without CPR (p=0.116). Conclusions In the current clinical practice, HU is effective in inducing CPR in about two thirds of patients with PV treated front-line. CPR is more frequently achieved by patients with lower disease burden, including lower WBC count, and less frequent PHL need and palpable spleen. Notably, >25% of responding patients achieved CPR after >12 months from HU start, suggesting the need for a long period of HU therapy before efficacy evaluation. The clinical importance of CPR is highlighted by a significantly longer EFS in patients achieving this type of response. Disclosures Breccia: Abbvie: Consultancy; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Benevolo:Amgen: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Cavazzini:Pfize: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Heidel:Novartis: Consultancy, Honoraria, Research Funding. Crugnola:Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria. Pane:AbbVie: Consultancy, Other: Travel Expenses, Speakers Bureau; Amgen: Consultancy, Other: Travel Expenses, Speakers Bureau; Daiichi Sankyo: Consultancy, Other: Travel Expenses; Jazz Pharmaceuticals: Consultancy, Other: travel expenses, Speakers Bureau; Novartis pharma SAS: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Other: Travel Expenses; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cuneo:Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra Zeneca: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Krampera:Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Semenzato:Abbvie: Honoraria; Roche: Honoraria; Takeda: Honoraria. Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Palumbo:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Palandri:Novartis: Consultancy, Honoraria.
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- 2020
48. Determinants of Choice of Front-Line Tyrosine Kinase Inhibitor for Chronic Phase CML: A Study from the 'Registro Italiano LMC & Campus CML'
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Giovanni Caocci, Anna Rita Scortechini, Federica Sorà, Concettina Ruggiero, Sabrina Leonetti Crescenzi, Massimiliano Bonifacio, Rosaria Sancetta, Sabina Russo, Alessandro Maggi, Gianni Binotto, Elena Crisà, Alessandra Iurlo, Giuseppe Saglio, Massimo Breccia, Annapaola Leporace, Maria Cristina Miggiano, Roberto Latagliata, Francesco Cavazzini, Mario Annunziata, Isabella Capodanno, Mario Tiribelli, Pamela Murgano, Giuseppina Loglisci, and Giorgina Specchia
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medicine.medical_specialty ,medicine.drug_class ,business.industry ,Immunology ,Imatinib ,Cell Biology ,Hematology ,Biochemistry ,Tyrosine-kinase inhibitor ,Dasatinib ,Nilotinib ,Interquartile range ,Concomitant ,Internal medicine ,Cohort ,medicine ,business ,Sokal Score ,medicine.drug - Abstract
Introduction : therapy of chronic phase (CP) chronic myeloid leukemia (CML) is based on tyrosine kinase inhibitors (TKIs) in virtually all patients. Three TKIs are approved for first-line therapy in Italy: imatinib and two second-generation (2G) TKIs, dasatinib and nilotinib. Choice of the front-line TKI is based on a combined evaluation of patient's and disease characteristics, age, risk, comorbidities and concomitant medications. Treating physician's preference and, in some cases, economic considerations, particularly after the advent of generic imatinib, may play a role in TKI selection. However, to date, few data are available on TKI use in a whole nation and on the possible drivers of treatment choice. Aim of the present work was to analyse the use of front-line TKI therapy in a large, unselected cohort of Italian CP-CML patients, correlating patient's features to drug choice. Methods: in the framework of the national Campus CML program, we retrospectively evaluated 1422 patients with CP-CML diagnosed from 2012 and 2019 in 21 haematologic Centres, mostly in academic and/or tertiary hospitals, widespread through the entire Italian territory and treated frontline with imatinib, dasatinib or nilotinib. Results: median age at diagnosis was 59.9 years [interquartile range (IQR) 47.1 - 71.7], with 317 (22.3%) patients under 45 years, 552 (38.8%) between 45 and 65 years and 553 (38.9%) older than 65 years; 821 (57.7%) patients were males. Among 1364 evaluable patients, CML risk according to Sokal score was low in 540 (39.6%), intermediate in 610 (44.7%) and high in 214 (15.7%) patients respectively; the number at low, intermediate or high risk according to the novel ELTS score among 1325 evaluable patients was 759 (57.3%), 402 (30.3%) and 164 (12.4%) respectively. Considering comorbidities, 1003 (70.6%) patients had at least one active disease at the time of CML diagnosis, the most common being hypertension (n=547, 38.5%), previous neoplasms (n=185, 13.0%), diabetes (n=150, 10.6%), chronic bronchopulmonary diseases (n=114, 8.0%), acute myocardial infarction (n=95, 6.7%), previous stroke (n=36, 2.5%) and other vascular diseases (n=98, 6.9%). Among 1335 evaluable patients, 813 (60.9%) were taking at least one concomitant medication, with 280 (21.0%) taking 3-5 drugs and 140 (10.5%) taking 6+ drugs at time of TKI start. As to the frontline therapy, 794 (55.8%) received imatinib and 628 (44.2%) were treated with 2G-TKIs, (226 dasatinib and 402 nilotinib) respectively. According to age, 2G-TKIs were chosen for majority of patients aged 100,000/mm3 vs 38.2% if WBC 10 g/dl; p=0.001) and bigger spleen (65.1% if spleen >5 cm vs 44.8% if spleen 1-5 cm vs 37.3% if spleen not palpable; p5 drugs, respectively (p 45 years, intermediate or high Sokal risk, presence of some comorbidities (2nd neoplasia and stroke) and number of concomitant medications. Conclusions: preliminary results of this observational study on almost 1500 patients show that around 55% of newly diagnosed Italian CP-CML patients receive imatinib as front-line therapy, and that the use of 2G-TKI is prevalent in the younger patients and in those with no concomitant clinical conditions. The counterintuitive finding of imatinib prevalence as frontline treatment in high risk patients might be explained by the older age of these patients. Introduction of the generic formulation in 2018 seems to have fostered the use of imatinib. Figure Disclosures Breccia: Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Abbvie: Consultancy; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria. Cavazzini:Pfize: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Saglio:Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding; Incyte: Research Funding; Novartis: Research Funding; Ariad: Research Funding; Roche: Research Funding.
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- 2020
49. Ruxolitinib in elderly patients with myelofibrosis: impact of age and genotype. A multicentre study on 291 elderly patients
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G. Semenzato, Massimiliano Bonifacio, Mario Tiribelli, Daniela Bartoletti, Lucia Catani, Bruno Martino, Micaela Bergamaschi, Florian H. Heidel, Giuseppe A. Palumbo, Gianni Binotto, Francesca Palandri, Antonio Cuneo, Mariella D'Adda, Michele Cavo, Alessandra Iurlo, Massimo Breccia, Alessandro Isidori, Elena Sabattini, Maria Rosaria Sapienza, Nicola Polverelli, Giulia Benevolo, Roberto M. Lemoli, Nicola Sgherza, Umberto Vitolo, Monica Crugnola, Elisabetta Abruzzese, Adalberto Ibatici, Nicola Vianelli, Costanza Bosi, Franco Aversa, Roberto Latagliata, Francesco Cavazzini, Alessia Tieghi, Giovanni Martinelli, Francesca Palandri, Lucia Catani, Massimiliano Bonifacio, Giulia Benevolo, Florian Heidel, Giuseppe A. Palumbo, Monica Crugnola, Elisabetta Abruzzese, Daniela Bartoletti, Nicola Polverelli, Micaela Bergamaschi, Mario Tiribelli, Alessandra Iurlo, Massimo Breccia, Francesco Cavazzini, Alessia Tieghi, Gianni Binotto, Alessandro Isidori, Bruno Martino, Mariella D'Adda, Costanza Bosi, Elena Sabattini, Umberto Vitolo, Franco Aversa, Adalberto Ibatici, Roberto M. Lemoli, Nicola Sgherza, Antonio Cuneo, Giovanni Martinelli, Giampietro Semenzato, Michele Cavo, Nicola Vianelli, Maria R. Sapienza, and Roberto Latagliata
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0301 basic medicine ,elderly ,high molecular risk ,high molecular risk mutations ,myelofibrosis ,ruxolitinib ,Ruxolitinib ,medicine.medical_specialty ,Genotype ,Socio-culturale ,Hematology ,Older population ,03 medical and health sciences ,0302 clinical medicine ,myelofibrosi ,Older patients ,Risk Factors ,Internal medicine ,Nitriles ,Medicine ,Humans ,Myelofibrosis ,Aged ,Janus Kinases ,Retrospective Studies ,business.industry ,Age Factors ,elderly, high molecular risk, high molecular risk mutations, myelofibrosis, ruxolitinib ,medicine.disease ,Mutation ,Primary Myelofibrosis ,Pyrazoles ,Survival Analysis ,Treatment Outcome ,Peripheral blood ,Discontinuation ,030104 developmental biology ,Pyrimidines ,030220 oncology & carcinogenesis ,high molecular risk mutation ,business ,medicine.drug - Abstract
Ruxolitinib is a JAK1/2 inhibitor that may control myelofibrosis (MF)-related splenomegaly and symptoms and can be prescribed regardless of age. While aging is known to correlate with worse prognosis, no specific analysis is available to confirm that ruxolitinib is suitable for use in older populations. A clinical database was created in 23 European Haematology Centres and retrospective data on 291 MF patients treated with ruxolitinib when aged ≥65 years were analysed in order to assess the impact of age and molecular genotype on responses, toxicities and survival. Additional mutations were evaluated by a next generation sequencing (NGS) approach in 69 patients with available peripheral blood samples at the start of ruxolitinib treatment. Compared to older (age 65-74 years) patients, elderly (≥75 years) showed comparable responses to ruxolitinib, but higher rates of drug-induced anaemia and thrombocytopenia and worse survival. Nonetheless, the ruxolitinib discontinuation rate was comparable in the two age groups. Number and types of molecular abnormalities were comparable across age groups. However, the presence of high molecular risk (HMR) mutations significantly affected survival, counterbalancing the effect of aging. Indeed, elderly patients with
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- 2018
50. An extensive molecular cytogenetic characterization in high-risk chronic lymphocytic leukemia identifies karyotype aberrations and TP53 disruption as predictors of outcome and chemorefractoriness
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Elisa Tammiso, Massimo Negrini, Elena Saccenti, Eleonora Volta, Laura Lupini, Enrico Lista, Francesca Maria Quaglia, Antonio Urso, Francesco Cavazzini, Maurizio Cavallari, Cristian Bassi, Antonio Cuneo, Aurora Melandri, Luca Formigaro, Sara Martinelli, Maria Antonella Bardi, Gian Matteo Rigolin, and Emanuele Guardalben
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Multivariate analysis ,Chronic lymphocytic leukemia ,Biology ,Tp53 mutation ,medicine.disease_cause ,NO ,03 medical and health sciences ,0302 clinical medicine ,Next generation sequencing ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Complex Karyotype ,CLL, prognosis, karyotype, TP53 ,medicine ,Humans ,TP53 ,Gene somatic mutations ,Stage (cooking) ,Aged ,Aged, 80 and over ,Chromosome Aberrations ,Genetics ,Mutation ,Karyotype ,Middle Aged ,Prognosis ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,karyotype ,Treatment Outcome ,Karyotype: prognosis ,030220 oncology & carcinogenesis ,Female ,Tumor Suppressor Protein p53 ,IGHV@ ,CLL ,Research Paper ,030215 immunology - Abstract
We investigated whether karyotype analysis and mutational screening by next generation sequencing could predict outcome in 101 newly diagnosed chronic lymphocytic leukemia patients with high-risk features, as defined by the presence of unmutated IGHV gene and/or 11q22/17p13 deletion by FISH and/or TP53 mutations. Cytogenetic analysis showed favorable findings (normal karyotype and isolated 13q14 deletion) in 30 patients, unfavorable (complex karyotype and/or 17p13/11q22 deletion) in 34 cases and intermediate (all other abnormalities) in 36 cases. A complex karyotype was present in 21 patients. Mutations were detected in 56 cases and were associated with unmutated IGHV status (p = 0.040) and complex karyotype (p = 0.047). TP53 disruption (i.e. TP53 mutations and/or 17p13 deletion by FISH) correlated with the presence of ≥ 2 mutations (p = 0.001) and a complex karyotype (p = 0.012). By multivariate analysis, an advanced Binet stage (p < 0.001) and an unfavorable karyotype (p = 0.001) predicted a shorter time to first treatment. TP53 disruption (p = 0.019) and the unfavorable karyotype (p = 0.028) predicted a worse overall survival. A shorter time to chemorefractoriness was associated with TP53 disruption (p = 0.001) and unfavorable karyotype (p = 0.025). Patients with both unfavorable karyotype and TP53 disruption presented a dismal outcome (median overall survival and time to chemorefractoriness of 28.7 and 15.0 months, respectively). In conclusion, karyotype analysis refines risk stratification in high-risk CLL patients and could identify a subset of patients with highly unfavorable outcome requiring alternative treatments.
- Published
- 2017
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