579 results on '"Guarini, A."'
Search Results
2. Impact of COVID-19 Pandemic Waves on Outcomes of Patients with Previously Untreated Advanced Follicular Lymphoma Enrolled in the Urban Ambispective Study in Italy
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Antonio Pinto, Emanuele Guardalben, Marica Battista, Giulia Chiara Gazzoli, Michele Merli, Annalisa Chiarenza, Tommasina Perrone, Attilio Guarini, Nicola Di Renzo, Carlo Visco, Agostino Tafuri, Roberta Murru, Felicetto Ferrara, Jacopo Olivieri, Attilio Olivieri, Andrés J M Ferreri, Marco Ladetto, Pier Luigi Zinzani, Luca Arcaini, and Giuseppe Gritti
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
3. Real-World Outcome of Treatment with Single-Agent Ibrutinib in Patients with Chronic Lymphocytic Leukemia: Results from the Italian Study Evidence
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Stefano Molica, Potito Rosario Scalzulli, Lydia Scarfò, Attilio Guarini, Roberta Murru, Paolo Sportoletti, Ferdinando Frigeri, Francesco Albano, Nicola Di Renzo, Alessandro Sanna, Idanna Innocenti, Massimo Massaia, Marta Coscia, Elsa Pennese, Caterina Patti, Gianluigi Reda, Agostino Tafuri, Giulia Regazzoni, Michele Di Candia, and Francesca Romana Mauro
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
4. Endothelial-leukemia interactions remodel drug responses uncovering T-ALL vulnerabilities
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Luca Vincenzo Cappelli, Danilo Fiore, Jude M. Phillip, Liron Yoffe, Filomena Di Giacomo, William Chiu, Yang Hu, Clarisse Kayembe, Michael Ginsberg, Lorena Consolino, Jose Gabriel Barcia Duran, Nahuel Zamponi, Ari M. Melnick, Francesco Boccalatte, Wayne Tam, Olivier Elemento, Sabina Chiaretti, Anna Guarini, Robin Foà, Leandro Cerchietti, Shahin Rafii, Giorgio Inghirami, Cappelli, L. V., Fiore, D., Phillip, J. M., Yoffe, L., Di Giacomo, F., Chiu, W., Hu, Y., Kayembe, C., Ginsberg, M., Consolino, L., Barcia Duran, J. G., Zamponi, N., Melnick, A. M., Boccalatte, F., Tam, W., Elemento, O., Chiaretti, S., Guarini, A., Foa, R., Cerchietti, L., Rafii, S., and Inghirami, G.
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and often incurable disease. To uncover therapeutic vulnerabilities, we first developed T-ALL patient–derived tumor xenografts (PDXs) and exposed PDX cells to a library of 433 clinical-stage compounds in vitro. We identified 39 broadly active drugs with antileukemia activity. Because endothelial cells (ECs) can alter drug responses in T-ALL, we developed an EC/T-ALL coculture system. We found that ECs provide protumorigenic signals and mitigate drug responses in T-ALL PDXs. Whereas ECs broadly rescued several compounds in most models, for some drugs the rescue was restricted to individual PDXs, suggesting unique crosstalk interactions and/or intrinsic tumor features. Mechanistically, cocultured T-ALL cells and ECs underwent bidirectional transcriptomic changes at the single-cell level, highlighting distinct “education signatures.” These changes were linked to bidirectional regulation of multiple pathways in T-ALL cells as well as in ECs. Remarkably, in vitro EC-educated T-ALL cells transcriptionally mirrored ex vivo splenic T-ALL at single-cell resolution. Last, 5 effective drugs from the 2 drug screenings were tested in vivo and shown to effectively delay tumor growth and dissemination thus prolonging overall survival. In sum, we developed a T-ALL/EC platform that elucidated leukemia-microenvironment interactions and identified effective compounds and therapeutic vulnerabilities.
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- 2022
5. Real-World Outcome of Treatment with Single-Agent Ibrutinib in Patients with Chronic Lymphocytic Leukemia: Results from the Italian Study Evidence
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Molica, Stefano, primary, Scalzulli, Potito Rosario, additional, Scarfò, Lydia, additional, Guarini, Attilio, additional, Murru, Roberta, additional, Sportoletti, Paolo, additional, Frigeri, Ferdinando, additional, Albano, Francesco, additional, Di Renzo, Nicola, additional, Sanna, Alessandro, additional, Innocenti, Idanna, additional, Massaia, Massimo, additional, Coscia, Marta, additional, Pennese, Elsa, additional, Patti, Caterina, additional, Reda, Gianluigi, additional, Tafuri, Agostino, additional, Regazzoni, Giulia, additional, Di Candia, Michele, additional, and Mauro, Francesca Romana, additional
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- 2022
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6. Validation of Argo (Automatic record generator for Onco-Hematology), a New App Supporting the Automatic Conversion of Paper-Based Pathology Reports in Standardized Ecrfs
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Zaccaria, Gian Maria, primary, Berloco, Francesco, additional, Clemente, Felice, additional, Pappagallo, Anita Susanna, additional, Vegliante, Maria Carmela, additional, Gargano, Grazia, additional, Mondelli, Paolo, additional, Volpe, Giacomo, additional, Bucci, Antonella, additional, Skrypets, Tetiana, additional, Minoia, Carla, additional, Quinto, Angela Maria, additional, Loseto, Giacomo, additional, Rossini, Bernardo, additional, Pavone, Fabio, additional, Scattone, Anna, additional, Carella, Giuseppe, additional, Angiulli, Vito, additional, Pagani, Chiara, additional, Di Rocco, Alice, additional, Quaglia, Francesca Maria, additional, Tabanelli, Valentina, additional, Fama, Angelo, additional, Puccini, Benedetta, additional, Moia, Riccardo, additional, Ferrero, Simone, additional, Grieco, Luigi Alfredo, additional, Colucci, Simona, additional, Guarini, Attilio, additional, and Ciavarella, Sabino, additional
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- 2022
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7. Impact of COVID-19 Pandemic Waves on Outcomes of Patients with Previously Untreated Advanced Follicular Lymphoma Enrolled in the Urban Ambispective Study in Italy
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Pinto, Antonio, primary, Guardalben, Emanuele, additional, Battista, Marica, additional, Gazzoli, Giulia Chiara, additional, Merli, Michele, additional, Chiarenza, Annalisa, additional, Perrone, Tommasina, additional, Guarini, Attilio, additional, Di Renzo, Nicola, additional, Visco, Carlo, additional, Tafuri, Agostino, additional, Murru, Roberta, additional, Ferrara, Felicetto, additional, Olivieri, Jacopo, additional, Olivieri, Attilio, additional, Ferreri, Andrés J M, additional, Ladetto, Marco, additional, Zinzani, Pier Luigi, additional, Arcaini, Luca, additional, and Gritti, Giuseppe, additional
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- 2022
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8. Risk of Unemployment Among Chronic Myeloproliferative Disorders Patients
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Ditonno, Paolo, primary, DI Lorenzo, Luigi, additional, Pipoli, Antonella, additional, Minoia, Carla, additional, DI Somma, Ilaria Maria, additional, Lagattolla, Fulvia, additional, Romito, Francesca, additional, D'alonzo, Maria Giorgia, additional, Laddaga, Emanuela Filomena, additional, De Fazio, Vincenza, additional, and Guarini, Attilio, additional
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- 2022
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9. A Digital Gene-Expression Signature Supports Mediastinal Gray Zone Lymphoma Stratification within Classical Hodgkin or Primary Mediastinal B-Cell Lymphoma
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Vegliante, Maria Carmela, primary, Gargano, Grazia, additional, Esposito, Flavia, additional, Opinto, Giuseppina, additional, Zaccaria, Gian Maria, additional, Pappagallo, Susanna Anita, additional, Mondelli, Paolo, additional, Loseto, Giacomo, additional, Scattone, Anna, additional, Sabattini, Elena, additional, Agostinelli, Claudio, additional, Tabanelli, Valentina, additional, Nassi, Luca, additional, Guarini, Attilio, additional, Pileri, Stefano A, additional, and Ciavarella, Sabino, additional
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- 2022
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10. Oral Antiviral Therapy and Monoclonal Antibody for the Treatment of COVID-19 Infection in Outpatients Receiving Anti-Cancer Treatment for Hematological Malignancies: A Multicenter Prospective Study Exploring Efficacy, Safety and Predictors of COVID-19 Lung Failure
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Minoia, Carla, primary, Bavaro, Davide, additional, Loseto, Giacomo, additional, Pasciolla, Crescenza, additional, Diella, Lucia, additional, Pelligrino, Carmen, additional, Totaro, Valentina, additional, Spada, Vito, additional, Camporeale, Michele, additional, Attolico, Immacolata, additional, Perrone, Tommasina, additional, Clemente, Felice, additional, di Gennaro, Francesco, additional, Musto, Pellegrino, additional, Guarini, Attilio, additional, and Saracino, Annalisa, additional
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- 2022
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11. Complex karyotype in unfit patients with CLL treated with ibrutinib and rituximab: the GIMEMA LLC1114 phase 2 study
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Ilaria Del Giudice, Livio Trentin, Valentina Arena, Monia Marchetti, Caterina Ilari, Rocio Edith García-Jacobo, Gian Matteo Rigolin, Aurora Melandri, Luciana Cafforio, Robin Foà, Gianluigi Reda, Francesca Romana Mauro, Alfonso Piciocchi, Francesca Cura, Francesco Albano, Sara Raponi, Stefano Molica, Paola Mariglia, Anna Guarini, Antonio Cuneo, Maria Antonella Bardi, Mauro Nanni, Nadia Peragine, Marco Vignetti, and Paolo Sportoletti
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Phases of clinical research ,Cell Biology ,Hematology ,Biochemistry ,NO ,chemistry.chemical_compound ,COMPLEX KARYOTYPE ,chemistry ,Internal medicine ,Ibrutinib ,Complex Karyotype ,Medicine ,Rituximab ,RITUXIMAB ,IBRUTINIB ,business ,UNFIT PATIENTS ,COMPLEX KARYOTYPE, UNFIT PATIENTS, CLL, IBRUTINIB, RITUXIMAB ,CLL ,medicine.drug - Published
- 2021
12. Host immune system modulation in Ph+ acute lymphoblastic leukemia patients treated with dasatinib and blinatumomab
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Paola Mariglia, Marco Vignetti, Robin Foà, Antonella Vitale, Gianluca Gaidano, Maria Stefania De Propris, Maria Cristina Puzzolo, Anna Guarini, Giulia Radice, Nadia Peragine, Sabina Chiaretti, Renato Bassan, Alessandro Rambaldi, and Mario Annunziata
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Adult ,business.industry ,Immunology ,Dasatinib ,Cell Biology ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Biochemistry ,Ph+ acute lymphoblastic leukemia ,Antineoplastic Agents, Immunological ,Immune system ,Immune System ,Antibodies, Bispecific ,Antineoplastic Combined Chemotherapy Protocols ,Cancer research ,Humans ,Medicine ,Philadelphia Chromosome ,Blinatumomab ,business ,Protein Kinase Inhibitors ,medicine.drug - Published
- 2021
13. Genetic lesions associated with chronic lymphocytic leukemia chemo-refractoriness
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Messina, Monica, Del Giudice, Ilaria, Khiabanian, Hossein, Rossi, Davide, Chiaretti, Sabina, Rasi, Silvia, Spina, Valeria, Holmes, Antony B., Marinelli, Marilisa, Fabbri, Giulia, Piciocchi, Alfonso, Mauro, Francesca R., Guarini, Anna, Gaidano, Gianluca, Dalla-Favera, Riccardo, Pasqualucci, Laura, Rabadan, Raul, and Foà, Robin
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- 2014
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14. Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia
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Rossi, Davide, Khiabanian, Hossein, Spina, Valeria, Ciardullo, Carmela, Bruscaggin, Alessio, Famà, Rosella, Rasi, Silvia, Monti, Sara, Deambrogi, Clara, De Paoli, Lorenzo, Wang, Jiguang, Gattei, Valter, Guarini, Anna, Foà, Robin, Rabadan, Raul, and Gaidano, Gianluca
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- 2014
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15. Risk of Unemployment Among Chronic Myeloproliferative Disorders Patients
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Paolo Ditonno, Luigi DI Lorenzo, Antonella Pipoli, Carla Minoia, Ilaria Maria DI Somma, Fulvia Lagattolla, Francesca Romito, Maria Giorgia D'alonzo, Emanuela Filomena Laddaga, Vincenza De Fazio, and Attilio Guarini
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
16. Oral Antiviral Therapy and Monoclonal Antibody for the Treatment of COVID-19 Infection in Outpatients Receiving Anti-Cancer Treatment for Hematological Malignancies: A Multicenter Prospective Study Exploring Efficacy, Safety and Predictors of COVID-19 Lung Failure
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Carla Minoia, Davide Bavaro, Giacomo Loseto, Crescenza Pasciolla, Lucia Diella, Carmen Pelligrino, Valentina Totaro, Vito Spada, Michele Camporeale, Immacolata Attolico, Tommasina Perrone, Felice Clemente, Francesco di Gennaro, Pellegrino Musto, Attilio Guarini, and Annalisa Saracino
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
17. Dysfunctional Vγ9Vδ2 T cells are negative prognosticators and markers of dysregulated mevalonate pathway activity in chronic lymphocytic leukemia cells
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Coscia, Marta, Vitale, Candida, Peola, Silvia, Foglietta, Myriam, Rigoni, Micol, Griggio, Valentina, Castella, Barbara, Angelini, Daniela, Chiaretti, Sabina, Riganti, Chiara, Guarini, Anna, Drandi, Daniela, Ladetto, Marco, Bosia, Amalia, Foà, Robin, Battistini, Luca, Boccadoro, Mario, Fournié, Jean-Jacques, and Massaia, Massimo
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- 2012
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18. Disruption of BIRC3 associates with fludarabine chemorefractoriness in TP53 wild-type chronic lymphocytic leukemia
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Rossi, Davide, Fangazio, Marco, Rasi, Silvia, Vaisitti, Tiziana, Monti, Sara, Cresta, Stefania, Chiaretti, Sabina, Del Giudice, Ilaria, Fabbri, Giulia, Bruscaggin, Alessio, Spina, Valeria, Deambrogi, Clara, Marinelli, Marilisa, Famà, Rosella, Greco, Mariangela, Daniele, Giulia, Forconi, Francesco, Gattei, Valter, Bertoni, Francesco, Deaglio, Silvia, Pasqualucci, Laura, Guarini, Anna, Dalla-Favera, Riccardo, Foà, Robin, and Gaidano, Gianluca
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- 2012
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19. Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia
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Rossi, Davide, Rasi, Silvia, Fabbri, Giulia, Spina, Valeria, Fangazio, Marco, Forconi, Francesco, Marasca, Roberto, Laurenti, Luca, Bruscaggin, Alessio, Cerri, Michaela, Monti, Sara, Cresta, Stefania, Famà, Rosella, De Paoli, Lorenzo, Bulian, Pietro, Gattei, Valter, Guarini, Anna, Deaglio, Silvia, Capello, Daniela, Rabadan, Raul, Pasqualucci, Laura, Dalla-Favera, Riccardo, Foà, Robin, and Gaidano, Gianluca
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- 2012
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20. Host immune system modulation in Ph+ acute lymphoblastic leukemia patients treated with dasatinib and blinatumomab
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Puzzolo, Maria Cristina, primary, Radice, Giulia, additional, Peragine, Nadia, additional, de Propris, Maria Stefania, additional, Mariglia, Paola, additional, Vignetti, Marco, additional, Vitale, Antonella, additional, Bassan, Renato, additional, Annunziata, Mario, additional, Gaidano, Gianluca, additional, Rambaldi, Alessandro, additional, Chiaretti, Sabina, additional, Guarini, Anna, additional, and Foà, Robin, additional
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- 2021
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21. A Predictive Endothelial-Leukemia Pre-Clinical Platform to Uncover Drug Vulnerabilities for Personalized Treatments
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Cappelli, Luca Vincenzo, primary, Fiore, Danilo, additional, Phillip, Jude M, additional, Yoffe, Liron, additional, Di Giacomo, Filomena, additional, Hu, Yang, additional, Kayembe, Clarisse, additional, Ginsberg, Michael, additional, Consolino, Lorena, additional, Barcia Durán, José Gabriel, additional, Zamponi, Nahuel, additional, Melnick, Ari, additional, Boccalatte, Francesco, additional, Tam, Wayne, additional, Elemento, Olivier, additional, Chiaretti, Sabina, additional, Guarini, Anna, additional, Foa, Robin, additional, Cerchietti, Leandro, additional, Rafii, Shahin, additional, and Inghirami, Giorgio, additional
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- 2021
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22. The Use of Ibrutinib in Italian CLL Patients Treated in a Real-World Setting (EVIDENCE): A Preliminary Report
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Molica, Stefano, primary, Scalzulli, Potito Rosario, additional, Scarfo, Lydia, additional, Guarini, Attilio, additional, Murru, Roberta, additional, Sportoletti, Paolo, additional, Frigeri, Ferdinando, additional, Albano, Francesco, additional, Di Renzo, Nicola, additional, Sanna, Alessandro, additional, Innocenti, Idanna, additional, Massaia, Massimo, additional, Coscia, Marta, additional, Pennese, Elsa, additional, Patti, Caterina, additional, Reda, Gianluigi, additional, Tafuri, Agostino, additional, Grugnetti, Anna, additional, Magarotto, Valeria, additional, and Mauro, Francesca Romana, additional
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- 2021
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23. Efficacy and Safety of Front-Line Venetoclax and Rituximab (VenR) for the Treatment of Young Patients with Chronic Lymphocytic Leukemia and an Unfavorable Biologic Profile. Preliminary Results of the Gimema Study 'Veritas'
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Lydia Scarfò, I. Del Giudice, Gianluigi Reda, Marta Coscia, Roberta Murru, L. Orsucci, Daniela Pietrasanta, Caterina Stelitano, Ramona Cassin, Marina Deodato, Donato Mannina, Livio Trentin, Sara Raponi, Luciano Levato, Annalisa Arcari, Antonio Cuneo, Gian Matteo Rigolin, F. Ilariucci, Monica Tani, Valentina Arena, G. Giuliani, Stefano Molica, Anna Guarini, F.R. Mauro, Roberto Marasca, M.S. De Propris, Gianluca Gaidano, Gerardo Musuraca, Luca Laurenti, Anna Marina Liberati, G. Lapietra, Andrea Visentin, Daniela Gottardi, Antonino Neri, Catello Califano, Massimo Massaia, I. Della Starza, Paolo Sportoletti, Piero Galieni, Marco Vignetti, Robert Foa, Francesco Albano, Candida Vitale, Monia Marchetti, and Mauro Nanni
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Oncology ,medicine.medical_specialty ,Venetoclax ,business.industry ,Chronic lymphocytic leukemia ,Immunology ,Front line ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,Rituximab ,business ,medicine.drug - Abstract
Fixed-duration treatment with venetoclax (Ven), a highly selective Bcl-2 inhibitor combined with an anti-CD20 monoclonal antibody, showed high efficacy inducing high rates of deep responses with undetectable minimal residual disease (uMRD) in patients with previously treated and untreated chronic lymphocytic leukemia (CLL). The efficacy and safety of the Ven and rituximab (VenR) combination have been investigated in a multicenter, prospective study of the GIMEMA group that included young patients with previously untreated CLL (LLC 1518, VERITAS, NCT03455517). The primary endpoint of this study was the CR rate assessed according to the iwCLL criteria. Inclusion criteria were: treatment requirement per iwCLL criteria, age ≤65 years, cumulative Illness rating scale score ≤6, creatinine clearance ≥30 mL/min, and an unfavorable biologic profile with IGHV unmutated and or TP53 disruption. Treatment consisted of the Ven dose ramp-up (from 20 to 400 mg daily, during 5-weeks) followed by Ven 400 mg daily, combined with R for six 28-day courses (375 mg/m2, course 1; 500 mg/m2, courses 2-6). Patients continued with Ven single agent, 400 mg daily, until month 13. Tumor lysis syndrome (TLS) prophylaxis measures included hydration, allopurinol, or rasburicase. All patients received PneumocystisJirovecii prophylaxis. G-CSF was given in patients with recurrent and severe granulocytopenia. Adverse events (AEs) were graded according to the CTCAE criteria v.5, TLS events were classified according to Howard's criteria. Response was assessed at months 7 and 15 and included clinical examination, PB evaluation, BM aspirate, BM biopsy, and CT scan. MRD was checked centrally in the PB and BM by a 6/4-color flow-cytometry assay with a sensitivity of at least 10-4 according to the internationally standardized European Research Initiative on CLL. Quantitative MRD results assessed by flow-cytometry were categorized as uMRD (uMRD4; Between October 2018 and May 2020, 77 patients with CLL were included in this study. Two patients were off study before the start of treatment (withdrawal of consent, 1; Covid-19 infection, 1) and were not included in the analysis. The median age was 53.5 years (range 38-65). Binet stage B/C was present in 84% of patients, increased beta-2 microglobulin in 41%. Seventy-one (96%) of patients were IGHV unmutated, while 3 (4%) were IGHV mutated and showed TP53 mutation (Table 1). At the data cutoff of June 30, 2020, 65 (87%) patients completed the ramp-up phase. The planned 400 mg dose of Ven was reached within 5 weeks in 78.5% of patients. Response was assessed in 34 patients at the end of the VenR combination therapy. A response was achieved by 32 (94%) patients. Responses included 20 (59%) CRs, 1 CRi (3%) and 11 (32%) PRs due to residual enlarged nodes (median maximum size, 1.9 cm). Treatment failure due to toxicity was recorded in 2 (6%) patients. Overall, a response with uMRD4 by flow-cytometry in the PB was observed in 26 (76.5%) cases, and in the PB and BM, in 17 (50.0%). The rates of patients with CR and uMRD4 by flow-cytometry in the PB, and both in the PB and BM, were 44%, and 35%, respectively (Table 2). No detectable disease by PCR, both in the PB and BM, was observed in 4 (12%) patients. With a median follow-up of 4.5 months from the start of therapy, no patient has progressed or died. Fifty-three percent of patients were hospitalized during the first seven days of the Ven ramp-up phase. A transient laboratory TLS was observed in 3 patients. Treatment was discontinued after the first dose of Ven in 1 patient with evidence of laboratory TLS associated with severe neurologic toxicity due to the concomitant administration of fentanyl. Selected grade ≥3 AEs included neutropenia in 10 patients (ramp-up phase, 5) and neutropenic fever in 4. Grade ≥3 infection was recorded in 3 patients and was the reason for treatment discontinuation in 1 who developed COVID-19 pneumonia. In conclusion, the preliminary results of this study demonstrate the high efficacy of the front-line VenR combination, which resulted in a high proportion of CRs and responses with uMRD4 in young patients with CLL and an unfavorable biologic profile. Disclosures Mauro: Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jannsen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octopharma: Consultancy. Reda:Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Trentin:Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shire: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees. Coscia:Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Research Funding; Abbvie: Honoraria, 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, Research Funding, Speakers Bureau. Sportoletti: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. Laurenti:Roche: Membership on an entity's Board of Directors or advisory committees; AbbVie: 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; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gaidano:Astrazeneca: Membership on an entity's Board of Directors or advisory committees; 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; Sunesys: Membership on an entity's Board of Directors or advisory committees. Marasca:Abbvie: 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; Shire: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees. Murru:Gilead: 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. Rigolin:Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Scarfo:Abbvie: 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; AstraZeneca: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees. Marchetti:Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees. Levato:Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; 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. Galieni:Celgene: Honoraria; Takeda: Honoraria; AbbVie: Honoraria; Janssen: Honoraria. Liberati:Verastem: Research Funding; Onconova: Research Funding; Janssen: Honoraria, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria, Research Funding; Pfizer: Research Funding; Karyopharm: Research Funding; Morphosys: Research Funding; Novartis: Research Funding; GSK: Research Funding; Incyte: Honoraria; Oncopeptides: Research Funding; Takeda: Research Funding. Molica:Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: 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; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Visentin: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; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vitale:Janssen: Honoraria. Del Giudice:Janssen: Other: grant for meeting participation; Tolero: Membership on an entity's Board of Directors or advisory committees; Roche: Other: grant for meeting partecipation; AstraZeneca: Membership on an entity's Board of Directors or advisory committees. Cuneo:Abbvie: 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; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra Zeneca: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Foà:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees.
- Published
- 2020
24. COMPLEX KARYOTYPE IN UNFIT PATIENTS WITH CLL TREATED WITH IBRUTINIB AND RITUXIMAB. THE GIMEMA LLC1114 PHASE 2 STUDY
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Rigolin, Gian Matteo, primary, Del Giudice, Ilaria, additional, Bardi, Maria Antonella, additional, Melandri, Aurora, additional, García-Jacobo, Rocio Edith, additional, Cura, Francesca, additional, Raponi, Sara, additional, Ilari, Caterina, additional, Cafforio, Luciana, additional, Piciocchi, Alfonso, additional, Arena, Valentina, additional, Reda, Gianluigi, additional, Albano, Francesco, additional, Molica, Stefano, additional, Sportoletti, Paolo, additional, Trentin, Livio, additional, Marchetti, Monia, additional, Nanni, Mauro, additional, Peragine, Nadia, additional, Mariglia, Paola, additional, Vignetti, Marco, additional, Guarini, Anna Rita, additional, Mauro, Francesca Romana, additional, Foà, Robin, additional, and Cuneo, Antonio, additional
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- 2021
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25. Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic features of 9 cases
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Del Giudice, Ilaria, Chiaretti, Sabina, Tavolaro, Simona, De Propris, Maria Stefania, Maggio, Roberta, Mancini, Francesca, Peragine, Nadia, Santangelo, Simona, Marinelli, Marilisa, Mauro, Francesca Romana, Guarini, Anna, and Foà, Robin
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- 2009
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26. ATM-ATR–dependent up-regulation of DNAM-1 and NKG2D ligands on multiple myeloma cells by therapeutic agents results in enhanced NK-cell susceptibility and is associated with a senescent phenotype
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Soriani, Alessandra, Zingoni, Alessandra, Cerboni, Cristina, Iannitto, Maria Luisa, Ricciardi, Maria Rosaria, Di Gialleonardo, Valentina, Cippitelli, Marco, Fionda, Cinzia, Petrucci, Maria Teresa, Guarini, Anna, Foà, Robin, and Santoni, Angela
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- 2009
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27. Efficacy and Safety of Front-Line Venetoclax and Rituximab (VenR) for the Treatment of Young Patients with Chronic Lymphocytic Leukemia and an Unfavorable Biologic Profile. Preliminary Results of the Gimema Study ‘Veritas‘
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Mauro, Francesca Romana, Reda, Gianluigi, Arena, Valentina, Trentin, Livio, Coscia, Marta, Sportoletti, Paolo, Laurenti, Luca, Gaidano, Gianluca, Marasca, Roberto, Orsucci, Lorella, Murru, Roberta, Stelitano, Caterina, Ilariucci, Fiorella, Mannina, Donato, Massaia, Massimo, Rigolin, Gian Matteo, Scarfo, Lydia, Marchetti, Monia, Levato, Luciano, Tani, Monica, Arcari, Annalisa, Musuraca, Gerardo, Deodato, Marina, Galieni, Piero, Califano, Catello, Gottardi, Daniela, Liberati, Anna Marina, Pietrasanta, Daniela, Molica, Stefano, Cassin, Ramona, Visentin, Andrea, Vitale, Candida, Lapietra, Gianfranco, Della Starza, Irene, De Propris, Maria Stefania, Raponi, Sara, Nanni, Mauro, Del Giudice, Ilaria, Giuliani, Giorgia, Vignetti, Marco, Guarini, Anna, Albano, Francesco, Neri, Antonino, Cuneo, Antonio, and Foà, Robin
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- 2020
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28. BCR ligation induced by IgM stimulation results in gene expression and functional changes only in IgVH unmutated chronic lymphocytic leukemia (CLL) cells
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Guarini, Anna, Chiaretti, Sabina, Tavolaro, Simona, Maggio, Roberta, Peragine, Nadia, Citarella, Franca, Ricciardi, Maria Rosaria, Santangelo, Simona, Marinelli, Marilisa, De Propris, Maria Stefania, Messina, Monica, Mauro, Francesca Romana, Del Giudice, Ilaria, and Foà, Robert
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- 2008
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29. A Predictive Endothelial-Leukemia Pre-Clinical Platform to Uncover Drug Vulnerabilities for Personalized Treatments
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Lorena Consolino, Leandro Cerchietti, Sabina Chiaretti, Shahin Rafii, Francesco Boccalatte, Robin Foà, Yang Hu, Luca Vincenzo Cappelli, Filomena Di Giacomo, Michael Ginsberg, Olivier Elemento, Ari Melnick, Liron Yoffe, Wayne Tam, Danilo Fiore, Giorgio Inghirami, Nahuel Zamponi, Clarisse Kayembe, Jude M. Phillip, José Gabriel Barcia Durán, and Anna Guarini
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Oncology ,Drug ,medicine.medical_specialty ,business.industry ,media_common.quotation_subject ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Leukemia ,Internal medicine ,medicine ,business ,media_common - Abstract
Background. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with few innovative treatment options. This is also contributed by the lack of models capable of capturing the complexity of the tumor and its microenvironment. Aims. To identify patient-specific vulnerabilities and novel therapeutic strategies in T-ALL and interrogate the mechanisms of the crosstalk between leukemic and stromal elements. Methods. We established a drug-testing platform using patient-derived-tumor-xenografts (PDTX) and a mixed-culture approach using E4ORF1-transduced endothelial cells (ECs) (Seandel M et al, PNAS 2008) to overcome host-mediated chemoresistance. We performed functional experiments using total and single-cell RNA sequencing. Results. First, we established a battery of 22 T-ALL PDTX models that matched both phenotypically (immune-histochemistry, flow cytometry) and genotypically (TCR rearrangement, transcriptome) with the primary patients' samples. We then challenged these models (n=14 samples belonging to different PDTX and serial passages within each model) with a library of compounds (n=433) targeting redundant proteins (n=634). Unsupervised clustering and Principal Component Analysis (PCA) demonstrated two clusters of T-ALL samples based on differential drug susceptibility. We could at least partially correlate these differences to specific transcriptomic signatures predictive of drug response (Figure 1A). We then defined a group of pan-active compounds across all models (n=40), which we validated using an independent screening with/without ECs (Figure 1B). We found that ECs counteracted the activity of selected compounds (i.e. TSA, THZ1 and MLN2238). By PCA, we observed distinct response profiles based on different T-ALL models. We vectorized the EC-rescue and found that the direction was the same across all 3 models tested, indicating that it relied on similar mechanisms regardless of model identity. Based on the known role of IGF1-IGFR1 as a supportive EC-rescue axis (Medyouf H et al, J Exp Med 2011), we performed the same screening with/without recombinant IGFBP-7 (500 ng/mL), a decoy IGF1 molecule. Remarkably, IGFBP-7 completely or partially abrogated the EC-mediated rescue of selected compounds [enzastaurin (PKC-β inhibitor), SC144 (GP130 inhibitor), CHIR124 (Chk1 inhibitor) and YM155 (Survivin inhibitor)] (Figure 1B). Drugs not rescued by ECs (n=30) were considered positive hits and 5 of them (ruxolitinib, tofacitinib, panobinostat, bortezomib, irinotecan) ultimately proved to be effective in vivo in randomized pre-clinical trials either alone or in combination (Figure 1C). Our stepwise endothelial-leukemia platform led to the discovery of "public" and "private" vulnerabilities and the proof-of-principle of prediction-guided in vivo pre-clinical trials. We propose a list of compounds that could be readily translated into T-ALL clinical trials (Figure 1D). We finally proved the validity of our platform using other disease models (i.e. B and T-lymphoma PDTXs). Mechanistically, at single-cell resolution, in vitro interacting T-ALL cells and ECs underwent reciprocal transcriptome changes, with T-ALL shifting towards stemness/undifferentiation and ECs towards tumor-ECs (TECs) phenotypes. Furthermore, in vitro EC-educated T-ALL cells mimicked distinct T-ALL subsets of the leukemic spleen of corresponding PDTX mice (Figure 1E). Conclusions. These data demonstrate that our EC-T-ALL culture system simulates in vivo conditions, offering a robust platform to study drug response, leukemia-host interactions and cell plasticity. This approach will improve the pre-clinical predictability of novel drugs/combinations for T-ALL, as well as for other hematologic malignancies, and propel the development of patient-tailored treatments. Figure 1 Figure 1. Disclosures Melnick: Janssen Pharmaceuticals: Research Funding; Sanofi: Research Funding; Daiichi Sankyo: Research Funding; Epizyme: Consultancy; Constellation: Consultancy; KDAC Pharma: Membership on an entity's Board of Directors or advisory committees. Elemento: AstraZeneca: Research Funding; Freenome: Consultancy, Other: Current equity holder in a privately-held company; Volastra Therapeutics: Consultancy, Other: Current equity holder, Research Funding; Champions Oncology: Consultancy; Owkin: Consultancy, Other: Current equity holder; One Three Biotech: Consultancy, Other: Current equity holder; Eli Lilly: Research Funding; Johnson and Johnson: Research Funding; Janssen: Research Funding. Chiaretti: amgen: Consultancy; pfizer: Consultancy; novartis: Consultancy; Incyte: Consultancy. Cerchietti: Celgene: Research Funding; Bristol Myers Squibb: Research Funding.
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- 2021
30. The Use of Ibrutinib in Italian CLL Patients Treated in a Real-World Setting (EVIDENCE): A Preliminary Report
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Francesco Albano, Francesca Romana Mauro, Paolo Sportoletti, Massimo Massaia, Idanna Innocenti, Lydia Scarfò, Ferdinando Frigeri, Attilio Guarini, Valeria Magarotto, Marta Coscia, Agostino Tafuri, Elsa Pennese, Anna Grugnetti, Alessandro Sanna, Roberta Murru, Potito Rosario Scalzulli, Stefano Molica, Caterina Patti, Nicola Di Renzo, and Gianluigi Reda
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Preliminary report ,Internal medicine ,Ibrutinib ,medicine ,business - Abstract
Introduction Ibrutinib is the only once-daily Bruton's tyrosine kinase (BTK) inhibitor with significant survival benefit vs chemo- and /or immunotherapy in multiple phase 3 studies of patients (pts) with chronic lymphocytic leukemia (CLL). It has profoundly changed the treatment landscape of CLL with the longest follow-up. However, seven years (yrs) after ibrutinib was approved in Italy by regulatory agencies for CLL treatment, available data on the patterns of care of such pts in the setting of clinical practice is limited. Herein we present the first interim analysis (IA) of EVIdeNCE (ClinicalTrials.gov Identifier: NCT03720561), a multicenter, observational clinical study designed to describe the current management of pts receiving ibrutinib in real-world setting in Italy in terms of retention rate: the study's primary end point. Methods EVIDENCE 312 treatment-naïve (TN) 38% and relapsed/refractory (R/R) 62% pts with CLL according to the iwCLL diagnosis criteria observed at 39 Italian hematological institutions in the period between November 2018 and October 2019. Inclusion criteria were treatment with ibrutinib according to the European Summary of Product Characteristics as per routine clinical practice started within the previous 3 months. The purpose of this IA is to provide demographics and disease characteristics at baseline and a preliminary evaluation of ibrutinib retention rate after one year of follow-up, along with its safety profile. Results The median age of pts at the time of ibrutinib initiation was 71.0 yrs (range 41.0-89.0), with 60% ≥70 yrs, 63.2% male, and 90% with Eastern Cooperative Oncology Group (ECOG) performance 0-1. Baseline Rai stage 0-I, II, and III-IV accounted for 18.3%, 29.7% and 52.1% pts, respectively. Patients in stage IV were observed in 40% of the R/R and 27% in TN subgroup. Considering 120 pts with known mutational status, del(17p) and/or TP53 mutation were present in 50.0% of pts (TN=52.1%, R/R=48.6%), while IGHV was unmutated in 35.0% (TN=33.3% and R/R=36.15) and mutated in 15.0% (TN=14.6%, R/R=15.3%). At baseline, 62.9% of pts had comorbidities and 30.6% presented with a history of cardiovascular diseases (CVDs). A CIRS score ≥6 was observed in 28.5% of pts. The median time from CLL diagnosis to the start of ibrutinib was 5.1 yrs (TN 1.75 yrs vs R/R 7.27 yrs). At least 1 treatment-emergent adverse event (TEAE) of any grade was experienced by 70.7% of pts. Frequencies were as follows: infections (30.8%; COVID-19 infections 3.2%), arthralgia (10.8%), neutropenia (9.3%), fatigue (8.4%), diarrhea (7.7%), atrial fibrillation (7.4%; grade 3-4, 4.2%), fever (7.1%), rash (6.4%), anemia (6.1%) and hypertension (4.2%). Mild bleeding TEAEs were reported in 16.1% of pts with no major bleeding event. TEAEs were more frequent in the elderly (≥65 yrs) while no significant differences in the rate of TEAEs were recorded in TN and R/R pts (69.7% vs 71.4%, respectively). Serious TEAEs were reported in 21.9% of pts. Overall in intention to treat (ITT), 32 deaths (10%) were observed (TN=8, R/R=24). The most common causes of death were infections (3.5%) and progressive disease (PD) (1.9%). Permanent discontinuation was observed in 56 (18%) of the pts (TN=17.2%, R/R=18.7%) and it mostly occurred within the first 6 months. Main causes of discontinuation were toxicity (6.1%), PD (3.8%) or death (3.5%). Temporary interruptions (≤ 3 months without therapy and/or dose modifications) during the whole observation period occurred in 30.3% (TN=35.3%, R/R=27.2%) and 37.7% (TN=37.5%, R/R=37.8%) of pts, respectively, mainly determined by toxicity and clinical judgment. Finally, in this first IA after 17.3 months (range 1.1 - 27.0) median follow-up, the ibrutinib retention rate (calculated as the ratio between the number of patients who retained ibrutinib treatment over the total number of patients at risk) at 1-year was 81.9% [95% confidence interval (CI), 77.2% - 86.1%] with no difference between TN 83.2% (95% CI, 75.2% - 89.4%) and R/R 81.2% pts (95% CI, 74.9% - 86.4%). Conclusions EVIDENCE is the first real-world study of ibrutinib use in CLL clinical practice in Italy. Ibrutinib retention rate at one-year suggests a better knowledge and expertise of hematologists in the management of ibrutinib-related toxicities that may result in an improved long-term outcome of pts with CLL. Disclosures Molica: Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Astrazeneca: Honoraria. Scarfo: Astra Zeneca: Honoraria; Abbvie: Honoraria; Janssen: Honoraria, Other: Travel grants. Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation; Janssen: Consultancy, Honoraria. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Frigeri: Celgene: Consultancy, Speakers Bureau; Abbvie: Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Amgen: Speakers Bureau. Sanna: Janssen: Consultancy; Abbvie: Consultancy; Astra Zeneca: Consultancy. Coscia: Janssen: Honoraria, Other, Research Funding; AbbVie: Honoraria, Other; AstraZeneca: Honoraria; Gilead: Honoraria. Reda: Abbvie: Consultancy; Astra Zeneca: Consultancy; Beigene: Consultancy; Janssen: Consultancy. Tafuri: Novartis: Research Funding; Roche: Research Funding; Celgene: Research Funding. Grugnetti: Janssen: Current Employment. Magarotto: Janssen: Current Employment. Mauro: Tskeda: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria, Speakers Bureau.
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- 2021
31. Predictive Factors for Overall Survival in Chronic Myeloid Leukemia Patients: An Analysis By the Gimema Cml Italian Study
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Specchia, Giorgina, primary, Pregno, Patrizia, additional, Breccia, Massimo, additional, Monagheddu, Chiara, additional, Castagnetti, Fausto, additional, Bonifacio, Massimiliano, additional, Tiribelli, Mario, additional, Stagno, Fabio, additional, Caocci, Giovanni, additional, Martino, Bruno, additional, Luciano, Luigiana, additional, Pizzuti, Michele, additional, Gozzini, Antonella, additional, Scortechini, Anna Rita, additional, Albano, Francesco, additional, Bergamaschi, Micaela, additional, Capodanno, Isabella, additional, Patriarca, Andrea, additional, Fava, Carmen, additional, Rege Cambrin, Giovanna, additional, Sorà, Federica, additional, Galimberti, Sara, additional, Bocchia, Monica, additional, Binotto, Gianni, additional, Reddiconto, Giovanni, additional, Guarini, Attilio, additional, Maggi, Alessandro, additional, Sanpaolo, Grazia, additional, De Candia, Maria Stella, additional, Giai, Valentina, additional, Abruzzese, Elisabetta, additional, Miggiano, Maria Cristina, additional, Falzetti, Franca, additional, La Barba, Gaetano, additional, Pietrantuono, Giuseppe, additional, Guella, Anna, additional, Levato, Luciano, additional, Mulas, Olga, additional, Saccona, Fabio, additional, Rosti, Gianantonio, additional, Musto, Pellegrino, additional, Di Raimondo, Francesco, additional, Pane, Fabrizio, additional, Foà, Robin, additional, Baccarani, Michele, additional, Ciccone, Giovannino, additional, and Saglio, Giuseppe, additional
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- 2020
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32. Adult T-cell acute lymphoblastic leukemia: biologic profile at presentation and correlation with response to induction treatment in patients enrolled in the GIMEMA LAL 0496 protocol
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Vitale, Antonella, Guarini, Anna, Ariola, Cristina, Mancini, Marco, Mecucci, Cristina, Cuneo, Antonio, Pane, Fabrizio, Saglio, Giuseppe, Cimino, Giuseppe, Tafuri, Agostino, Meloni, Giovanna, Fabbiano, Francesco, Recchia, Anna, Kropp, Maria Grazia, Krampera, Mauro, Cascavilla, Nicola, Ferrara, Felicetto, Romano, Antonio, Mazza, Patrizio, Fozza, Claudio, Paoloni, Francesca, Vignetti, Marco, and Foà, Robin
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- 2006
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33. ZAP-70 expression in acute lymphoblastic leukemia: association with the E2A/PBX1 rearrangement and the pre-B stage of differentiation and prognostic implications
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Chiaretti, Sabina, Guarini, Anna, De Propris, Maria Stefania, Tavolaro, Simona, Intoppa, Stefania, Vitale, Antonella, Iacobelli, Simona, Elia, Loredana, Ariola, Cristina, Ritz, Jerome, and Foà, Robin
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- 2006
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34. Dasatinib-Blinatumomab Combination for the Front-Line Treatment of Adult Ph+ ALL Patients. Updated Results of the Gimema LAL2116 D-Alba Trial
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Chiaretti, Sabina, primary, Bassan, Renato, primary, Vitale, Antonella, primary, Elia, Loredana, primary, Piciocchi, Alfonso, primary, Puzzolo, Cristina, primary, Canichella, Martina, primary, Ferrara, Felicetto, primary, Lunghi, Monia, primary, Fabbiano, Francesco, primary, Bonifacio, Massimiliano, primary, Fracchiolla, Nicola, primary, Salutari, Prassede, primary, Mancino, Alessandra, primary, Vignetti, Marco, primary, Guarini, Anna, primary, Rambaldi, Alessandro, primary, and Foà, Robin, primary
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- 2019
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35. Phase II Multicenter, Not Comparative, Study of Multiple Doses of NEPA (netupitant + palonosetron) in Preventing Chemotherapy-Induced Nausea and Vomiting (CINV) in Non-Hodgkin Lymphoma Patients Eligible for Autologous Hematopoietic Stem Cell Transplantation Receiving Multiple Days / High Dose Chemotherapy Regimens
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Di Renzo, Nicola, primary, Musso, Maurizio, additional, Scimè, Rosanna, additional, Milone, Giuseppe, additional, Perrone, Tommasina, additional, De Risi, Clara, additional, Pastore, Domenico, additional, Guarini, Attilio, additional, Mengarelli, Andrea, additional, Benedetti, Fabio, additional, Mazza, Patrizio, additional, Capria, Vera, additional, Chiusolo, Patrizia, additional, Cupelli, Luca, additional, Federico, Vincenzo, additional, Bozzoli, Valentina, additional, Messa, Anna Rita, additional, and Specchia, Giorgina, additional
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- 2019
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36. Role of Blinatumomab in Minimal Residual Disease and Hematologic Relapsed/Refractory Adult Acute Lymphoblastic Leukemia Patients Treated over 5 Years. a Single Center Experience
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Ansuinelli, Michela, primary, Vitale, Antonella, additional, Pecoraro, Giovanna, additional, Capria, Saveria, additional, Trisolini, Silvia Maria, additional, Minotti, Clara, additional, Cartoni, Claudio, additional, Testi, Anna Maria, additional, Moleti, Maria Luisa, additional, Iori, Anna Paola, additional, Barberi, Walter, additional, Della Starza, Irene, additional, Elia, Loredana, additional, Mancini, Francesca, additional, De Propris, Maria Stefania, additional, Guarini, Anna, additional, Chiaretti, Sabina, additional, and Foà, Robin, additional
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- 2019
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37. EARLY STAGE Follicular Lymphoma: First Results of the FIL "Miro" Study, a Multicenter Phase II Trial Combining Local Radiotherapy and MRD-Driven Immunotherapy
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Pulsoni, Alessandro, primary, Tosti, Maria Elena, primary, Ferrero, Simone, primary, Luminari, Stefano, primary, Liberati, Anna Marina, primary, Cenfra, Natalia, primary, Renzi, Daniela, primary, Zanni, Emanuela, primary, Boccomini, Carola, primary, Ferreri, Andres JM, primary, Rattotti, Sara, primary, Zilioli, Vittorio Ruggero, primary, Bernuzzi, Patrizia, primary, Bolis, Silvia, primary, Musuraca, Gerardo, primary, Nassi, Luca, primary, Perrone, Tommasina, primary, Stelitano, Caterina, primary, Anastasia, Antonella, primary, Corradini, Paolo, primary, Partesotti, Giovanni, primary, Re, Francesca, primary, Cencini, Emanuele, primary, Mannarella, Clara, primary, Mannina, Donato, primary, Molinari, Anna Lia, primary, Tani, Monica, primary, Annechini, Giorgia, primary, Assanto, Giovanni Manfredi, primary, Grapulin, Lavinia, primary, Della Starza, Irene, primary, Cavalli, Marzia, primary, De Novi, Lucia Anna, primary, Ciabatti, Elena, primary, Mantoan, Barbara, primary, Guarini, Anna, primary, Arcaini, Luca, primary, Ricardi, Umberto, primary, Gattei, Valter, primary, Galimberti, Sara, primary, Ladetto, Marco, primary, Del Giudice, Ilaria, primary, and Foà, Robin, primary
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- 2019
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38. The Validation of the BCR/ABL1-like Predictor across Laboratories Shows Reproducibility of Results
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Chiaretti, Sabina, primary, Akram, Taherinasab, additional, Martina, Canichella, additional, Messina, Monica, additional, Piciocchi, Alfonso, additional, Šálek, Cyril, additional, Machova, Katerina, additional, Blagoevova, Katerina, additional, Ribera, Jordi, additional, Ribera, Josep-Maria, additional, Meggendorfer, Manja, additional, Haferlach, Claudia, additional, Guarini, Anna, additional, and Foà, Robin, additional
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- 2019
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39. IFN-α promotes the rapid differentiation of monocytes from patients with chronic myeloid leukemia into activated dendritic cells tuned to undergo full maturation after LPS treatment
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Gabriele, Lucia, Borghi, Paola, Rozera, Carmela, Sestili, Paola, Andreotti, Mauro, Guarini, Anna, Montefusco, Enrico, Foà, Robert, and Belardelli, Filippo
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- 2004
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40. Chronic lymphocytic leukemia patients with highly stable and indolent disease show distinctive phenotypic and genotypic features
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Guarini, Anna, Gaidano, Gianluca, Mauro, Francesca Romana, Capello, Daniela, Mancini, Francesca, De Propris, Maria Stefania, Mancini, Marco, Orsini, Enrica, Gentile, Massimo, Breccia, Massimo, Cuneo, Antonio, Castoldi, Gianluigi, and Foa, Robert
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- 2003
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41. Dasatinib-Blinatumomab Combination for the Front-Line Treatment of Adult Ph+ ALL Patients. Updated Results of the Gimema LAL2116 D-Alba Trial
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Felicetto Ferrara, Francesco Fabbiano, Loredana Elia, Antonella Vitale, Martina Canichella, Alessandro Rambaldi, Sabina Chiaretti, Monia Lunghi, Marco Vignetti, Cristina Puzzolo, Renato Bassan, Massimiliano Bonifacio, Alessandra Mancino, Nicola Stefano Fracchiolla, Prassede Salutari, Robin Foà, Anna Guarini, and Alfonso Piciocchi
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0301 basic medicine ,medicine.medical_specialty ,business.industry ,education ,Immunology ,Front line ,Cell Biology ,Hematology ,CNS Prophylaxis ,Biochemistry ,Mutational analysis ,Transplantation ,Dasatinib ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Family medicine ,Honorarium ,Medicine ,In patient ,Blinatumomab ,business ,health care economics and organizations ,030215 immunology ,medicine.drug - Abstract
Background. The management of adult patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL), including the elderly, has changed since the introduction of tyrosine kinase inhibitors (TKI). A significantly better survival is observed in patients who become minimal residual disease (MRD)-negative. Aims. To increase the rate of MRD-negative patients, we designed a front-line chemo-free induction-consolidation trial (D-ALBA, GIMEMA LAL2116) based on the combination of the second-generation TKI dasatinib with the bispecific monoclonal antibody blinatumomab. The primary endpoint of the study was the rate of patients who achieved a complete molecular remission (CMR) or a positive non-quantifiable (PNQ) disease after at least two cycles of blinatumomab. Secondary endpoints included disease-free survival (DFS), overall survival (OS), cumulative incidence of relapse (CIR) and safety. We also sought to evaluate the prognostic impact of additional genomic lesions - performed on diagnostic samples - and the potential changes in the immunologic compartment, in terms of T cells and T-regulatory cells (Tregs), evaluated by flow cytometry (CD3+/CD4+, CD3+/CD8+ and CD3+/CD4+/CD25+/FOXp3+, respectively). Methods. This multicenter phase II study enrolled Ph+ ALL patients aged 18 years or older, with no upper age limit. Prior to dasatinib, patients received a 7-day steroids pre-phase: steroids were continued for further 24 days and stopped at day 31. Dasatinib (140 mg/day) was administered as induction for 85 days. Thereafter, patients who obtained a complete hematologic response (CHR) received a post-induction consolidation treatment with blinatumomab at a flat dose of 28 μg/day. A minimum of 2 cycles was mandatory, while the administration of up to 3 additional cycles was allowed based on the response to blinatumomab and medical decision. Dasatinib was continued during treatment with blinatumomab. CNS prophylaxis was carried out during the whole treatment. Post-consolidation treatment was open. Results. Between May 2017 and January 2019, 63 patients have been enrolled. Median age was 54.5 years (range: 24.1-81.7), 54% were female, the median white blood cell count (WBC) was 42 x109/l (range: 0.63-63.5) and 65.1% carried the p190 fusion. Copy number aberration analysis showed that the most frequent lesion was, as expected, IKZF1 deletion (54%): 23.9% of patients were thus classified as IKZF1plus (i.e. IKZF1 and/or PAX5 and/or CDKN2A/B deletions). The median follow-up is 10 months (range: 0.9-21.5). So far, 61 patients have completed induction, 55 the 1st cycle of blinatumomab, 47 the 2nd cycle, 33 the 3rd, 26 the 4th and 17 the 5th. Two patients have gone off protocol for medical decision and toxicity, and 1 died during induction. At the end of the induction with dasatonib, 17/58 pts (29.3%) had a molecular response (6 CMR and 11 PNQ). At the primary endpoint (end of the 2nd cycle of blinatumomab), 27/47 (56.3%) had a molecular response (17 CMR and 10 PNQ). The rates of molecular responses further increased after subsequent cycles of blinatumomab: 65.7% after the 3rd cycle and 80% after the 4th cycle. ABL1 mutational analysis was carried out in 15 patients with evidence of a MRD increase: 8 cases were WT, while mutations were detected in 7 (6 T315I, and 1 E255K). All mutations but 1 occurred prior to the start of blinatumomab and all were "cleared" by blinatumomab. The analysis of the immunologic compartment carried out in 12 patients who completed all 5 cycles of blinatumomab showed a significant increase in the rate of CD8+ T cells (19.8% before the start of blinatumomab and 29% after the 5th cycle, p=0.04) and a significant reduction in the rate of Tregs (11% before blinatumomab and 3.7% after the 5th cycle, p=0.02). Overall, 5 relapses have been recorded (2 hematologic, 2 isolated CNS and 1 nodal). The 12-month OS and DFS are 94.2% and 87.8%. A significantly inferior DFS (61.4%, p=0.01) was observed in IKZF1plus cases: these patients were prone to develop deleterious mutations. So far, 12 patients have been allografted and no transplant-related mortality has been recorded. Conclusions. In the first chemo-free induction-consolidation protocol for adult Ph+ ALL patients of all ages based on a combination of a targeted and immunotherapeutic strategy, the rates of molecular responses and survival are highly promising; patients harboring IKZF1 plus represent, also in this setting, a clinical challenge. Disclosures Chiaretti: Pfizer: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees. Bassan:Amgen Inc.: Honoraria; Incyte: Honoraria; Pfizer: Honoraria; Shire: Honoraria. Bonifacio:BMS: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Incyte: Honoraria. Vignetti:Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Educational Training; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Educational Training. Rambaldi:Omeros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Pfizer: 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, Other: travel support, Speakers Bureau; Italfarmaco: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, travel support. Foà:Celltrion: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau.
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- 2019
42. The Validation of the BCR/ABL1-like Predictor across Laboratories Shows Reproducibility of Results
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Manja Meggendorfer, Josep-Maria Ribera, Jordi Ribera, Katerina Blagoevova, Alfonso Piciocchi, Claudia Haferlach, Katerina Machova, Taherinasab Akram, Canichella Martina, Cyril Šálek, Anna Guarini, Monica Messina, Robin Foà, and Sabina Chiaretti
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Reproducibility ,Cost effectiveness ,Computer science ,education ,Immunology ,Cell Biology ,Hematology ,Computational biology ,Biochemistry ,Bcr abl1 ,Platelet-Derived Growth Factor beta Receptor ,hemic and lymphatic diseases ,Quantitative Real-Time Polymerase Chain Reaction ,health care economics and organizations ,Protein overexpression - Abstract
Background BCR/ABL1-like (alias Ph-like) acute lymphoblastic leukemia (ALL) is a clinically challenging subgroup. Its incidence varies from 10% in children to 30% in adult ALL. The underlying genomic background, usually characterized by the presence of kinase activating lesions, opens the way to targeted treatment. However, one of the major issues of this subset is represented by the identification of a standardized assay for their recognition at diagnosis. Indeed, while gene expression profile (GEP) and next-generation sequencing (NGS) are efficient techniques to identify these cases, they are difficult to be implemented in the diagnostic routine. Our group previously developed a rapid, simple and cost-effective algorithm based on a quantitative real time-polymerase chain reaction (Q-RT-PCR) named "BCR/ABL1-like predictor". Briefly, the expression levels of 10 genes - NUDT4, SEMA6A, ADGRE5, SOCS2, JCHAIN, CRLF2, TP53INP1, CD99, IFITM1 and IFITM2 - are used to generate a score: cases with a score ≥-0.3 are classified as BCR/ABL1-like. Aims After developing the BCR/ABL1-like predictor, we sought to: further refine the ability of this model to correctly predict BCR/ABL1-like ALL by evaluating NGS and RNA-sequencing of BCR/ABL1-like and non-BCR/ABL1-like cases, and to define the incidence of specific lesions;evaluate the reproducibility of the predictor when performed in external laboratories or when samples with a known genetic background were analyzed in house by the predictor. Results NGS and RNA-sequencing were carried out in 28 BCR/ABL1-like cases: CRLF2 overexpression, was found 35.7% of cases, with 3 harboring a CRLF2 rearrangement and 1 with a concomitant CRLF2 mutation. Furthermore, 13 JAK/STAT pathway mutations - JAK1, n=5; JAK2, n=3; IL7R and CRLF2, n=2 each, JAK3, n=1 - were identified in 33.3% of cases. Finally, RNA-sequencing and/or FISH experiments of the BCR/ABL1-like ALL cases revealed 11 lesions: 5 ABL-class fusion genes (3 NUP214/ABL1, 1 ZC3HAV1/ABL2 and 1 EBF1/PDGFRB), 2 BCR/JAK2, 3 CRLF2-r and 1 DDX3X/USP9X. In order to verify the reproducibility of the predictor, a collaboration was started across Europe with the Institute of Hematology and Blood Transfusion (ÚHKT, Prague), Josep Carreras Leukaemia Research Institute (Barcelona) and Munich Leukemia Laboratory (Munich), through the exchange of material and/or data. The first collaboration was carried out with the ÚHKT and Josep Carreras Leukaemia Research Institute laboratories: 11 cDNA samples (from 1 μg of total RNA), previously studied by our laboratory and classified as BCR/ABL1-like (n=5) and non-BCR/ABL1-like (n=6) ALL were shipped blindly and evaluated for the model in these laboratories. The technical set-up was sent to each laboratory, consisting of experimental procedures, PCR protocol and the threshold for Q-RT-PCR analysis. We received the raw data (i.e. 2^(-ΔCt) values) and uploaded them in the on-line BCR/ABL1-like predictor tool. We had 100% concordance with the ÚHKT and 81.8% with the Josep Carreras Leukaemia Research Institute. The main discrepancies were with 2/5 BCR/ABL1-like cases resulted as non-BCR/ABL1-like in the external laboratory: 1 was a p210 BCR/ABL1-positive case, used as control, which proved borderline, and the second was a BCR/ABL1-like case that, on the other hand, was not studied for the genetic features. A further collaboration was carried out with the MLL laboratory: we received 12 RNA samples - already analyzed by NGS and FISH - for evaluation by the BCR/ABL1-like predictor. The BCR-ABL1-like predictor classified 5 cases as BCR/ABL1-like and 7 as non-BCR-ABL1-like: all 5 BCR/ABL1-like carried a typical signature, consisting of a CRLF2 rearrangement plus JAK/STAT pathway mutations. Discordant cases were represented by 2 non-BCR-ABL1-like cases: one had a CRLF2 rearrangement plus JAK/STAT mutations and the other an ABL1 rearrangement. It is important to underline that the latter case had a borderline score (-0.482). Thus, the concordance rate was 83.3%. Conclusions This study shows that the BCR/ABL1-like predictor is a valid and reproducible tool across laboratories to identify rapidly these cases, with the goal of introducing genetic-driven therapeutic approaches upfront. One critical aspect is represented by borderline cases: in these patients, NGS experiments are required to define the underlying genomic lesion. Further investigations are currently underway. Disclosures Chiaretti: Incyte: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees. Machova:Novartis: Consultancy; Incyte: Consultancy; BMS: Consultancy, Research Funding. Meggendorfer:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Foà:Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Speakers Bureau.
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- 2019
43. EARLY STAGE Follicular Lymphoma: First Results of the FIL 'Miro' Study, a Multicenter Phase II Trial Combining Local Radiotherapy and MRD-Driven Immunotherapy
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Alessandro Pulsoni, Valter Gattei, Sara Galimberti, Antonella Anastasia, Monica Tani, Tommasina Perrone, Patrizia Bernuzzi, Giovanni Partesotti, Marzia Cavalli, Carola Boccomini, Lucia Anna De Novi, Clara Mannarella, Luca Nassi, Caterina Stelitano, Marco Ladetto, Natalia Cenfra, Giorgia Annechini, Sara Rattotti, Emanuele Cencini, Maria Elena Tosti, Anna Lia Molinari, Barbara Mantoan, Luca Arcaini, Paolo Corradini, Daniela Renzi, Elena Ciabatti, Anna Guarini, Robin Foà, Silvia Bolis, Irene Della Starza, Ilaria Del Giudice, Vittorio Ruggero Zilioli, Stefano Luminari, Andrés J.M. Ferreri, Gerardo Musuraca, Giovanni Manfredi Assanto, Francesca Re, Simone Ferrero, Anna Marina Liberati, Umberto Ricardi, Donato Mannina, Lavinia Grapulin, and Emanuela Zanni
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Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Chronic lymphocytic leukemia ,Immunology ,Follicular lymphoma ,Phases of clinical research ,Cell Biology ,Hematology ,Immunotherapy ,medicine.disease ,Ofatumumab ,Biochemistry ,Radiation therapy ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,Combined Modality Therapy ,Stage (cooking) ,business - Abstract
Introduction Limited stage follicular lymphoma (FL) is usually managed with involved field radiotherapy (IFRT), although different approaches are currently carried out, ranging from watch and wait to combined treatment. RT on involved lymph nodes allows eradication of the disease only in 40-50% of patients. Anti-CD20 monoclonal antibodies (MoAb), widely used in advanced stage FL, are likely to be effective in reducing the relapse risk, although no scientific evidence of their role has been provided. The aim of this multicenter phase II prospective study was to evaluate the role of MRD in identifying patients unlikely to be cured by RT, for whom an immunotherapy-based consolidation could improve outcome. Methods 110 patients with stage I/II FL were enrolled. IFRT was administered to all patients at a dose of 24 Gy. Peripheral blood (PB) and bone marrow (BM) samples were centralized to the Italian FIL (Federazione Italiani Linfomi) MRD Network of EuroMRD-certified laboratories: the presence of a BCL2/IGH rearrangement was investigated at baseline in all patients by nested PCR (NEST) and RQ-PCR (RQ), the latter according to the EuroMRD guidelines. In patients BCL2/IGH+ at baseline by both NEST and RQ in BM and/or PB, MRD was analyzed in both tissues after IFRT and every 6 months over a three-year follow-up period. Patients with positive MRD by both NEST and RQ in BM and/or PB after IFRT or who became positive during the follow-up were treated with 8 weekly doses of the anti-CD20 MoAb ofatumumab. The primary objective of the study was to define the efficacy of immunotherapy in obtaining the disappearance of BCL2/IGH rearranged cells. Results Preliminary data are available for 107 patients, 57 males, 50 females. Median age was 55 years (29-83). 17% had G1 FL, 32% G2, 40% G3A, 11% NOS. The FLIPI score was 0 in 59% of patients, 1 in 35%, 2 in 6%. 69% of patients had inguinal site involvement. Despite a negative BM biopsy, at baseline 30% of patients (n=32) had a BCL2/IGH rearrangement (30 MBR, 1 MBR and mcr, 1 mcr) in the BM and/or PB; the concordance between compartments was 90%, with 10% of negative PB showing a positive BM. No significant differences were observed in relapse probability between patients with or without a molecular marker. All patients were submitted to IFRT and all obtained a clinical response, which was complete in 79 of the 101 evaluated patients (78%) and partial in 22 (22%). MRD evaluation after treatment revealed the persistence of BCL2/IGH rearranged cells in the PB and/or BM in 60% of patients. According to the design of the protocol, MRD-positive patients, either after IFRT (n=18) or in case of conversion to a positive signal during the follow-up (n=7), received 8 weekly administration of ofatumumab. A conversion to MRD negativity, evaluated in 23 treated patients, was obtained in 20 (87% - CI 65.1-97.1). This result was significantly superior to the expected 50%. One death occurred after IFRT, due to ischemic stroke. Adverse events likely correlated to ofatumumab occurred in 7/25 treated patients, consisting of infusion reactions in 5, leading to a permanent interruption of immunotherapy in 3. After a median follow-up of 18 months, all patients who achieved a MRD negativity with ofatumumab underwent a regular molecular follow-up and are still MRD-negative. Overall, clinical relapse or progression were observed in 17 patients: 13 (18%) among the 73 "no marker" patients; 2 relapses (16%) were observed among the 12 MRD-negative patients after IFRT and 2 relapses were observed among the 23 patients treated with the anti-CD20 MoAb (8.7%), 1 having achieved a MRD negativity and 1 not. No significant differences in event-free survival have so far been observed between the three groups. Conclusions The MRD data of this phase II trial for early stage FL indicate that RT alone is often insufficient to eradicate the disease, being capable of inducing a negative MRD only in 40% of evaluable cases, with a long-lasting effect only in half of them. The primary objective of this study - MRD negativity after immunotherapy - was achieved, obtaining the disappearance of BCL2/IGH rearranged cells in the majority of patients treated with ofatumumab. The strategy of an immunotherapy consolidation after IFRT in MRD-positive patients allowed to increase molecular responses. A longer follow-up and further studies on larger patient populations will allow to conclusively define the impact of this MRD-driven strategy also on clinical outcome. Disclosures Pulsoni: Roche: Consultancy, Speakers Bureau; Takeda: Consultancy; Pfizer: Consultancy; Sandoz: Consultancy; Gilead: Speakers Bureau; Merk: Consultancy; Bristol Meyer Squibb: Speakers Bureau. Ferrero:Servier: Speakers Bureau; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees; Gilead: Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Luminari:ROCHE: Other: Role as Advisor ; CELGENE: Other: Role as Advisor & Travel Grant; TAKEDA: Other: Travel Grant; GILEAD: Other: Lecturer . Liberati:Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Celgene: Honoraria, Other: Clinical trial support; Bristol-Myers Squibb: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Janssen: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Roche: Other: Clinical trial support; Novartis: Other: Clinical trial support. Ferreri:Roche: Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Kite: Consultancy. Nassi:Takeda: Consultancy; Janssen: Consultancy; Merck: Consultancy. Corradini:Roche: Honoraria; Novartis: Honoraria; kite: Honoraria; KiowaKirin: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Daiichi Sankyo: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Servier: Honoraria; Sanofi: Honoraria; Takeda: Honoraria. Mannina:Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Arcaini:Celgene: Speakers Bureau; Gilead Sciences: Research Funding; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy; Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses. Galimberti:Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau. Ladetto:AbbVie: Honoraria; Roche: Honoraria; ADC Therapeutics: Honoraria; Acerta: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; J&J: Honoraria; Celgene: Honoraria. Foà:Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: The anti-CD20 MoAb Ofatumomab is employed to eradicate Minimal Residual Disease in early stage Follicular Lymphoma(FL). The drug is registered for Chronic Lymphocytic Leukemia, not for FL.
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- 2019
44. Role of Blinatumomab in Minimal Residual Disease and Hematologic Relapsed/Refractory Adult Acute Lymphoblastic Leukemia Patients Treated over 5 Years. a Single Center Experience
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Maria Stefania De Propris, Robin Foà, Anna Maria Testi, Irene Della Starza, Anna Guarini, Antonella Vitale, Maria Luisa Moleti, Sabina Chiaretti, Clara Minotti, Claudio Cartoni, Giovanna Pecoraro, Walter Barberi, Anna Paola Iori, Michela Ansuinelli, Francesca Mancini, Loredana Elia, Silvia Maria Trisolini, and Saveria Capria
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medicine.medical_specialty ,business.industry ,education ,Immunology ,Context (language use) ,Cell Biology ,Hematology ,Single Center ,medicine.disease ,Biochemistry ,Minimal residual disease ,Transplantation ,Clinical trial ,Internal medicine ,Acute lymphocytic leukemia ,Cohort ,medicine ,Blinatumomab ,business ,health care economics and organizations ,medicine.drug - Abstract
Background. Hematologic and, to a lesser extent, molecular relapsed/refractory in adult acute lymphoblastic leukemia (R/R ALL) is associated with a poor outcome, with low rates of subsequent complete remission (CR) and short survival. Blinatumomab has shown to be effective in both settings. Aims and methods. In this retrospective, single center study we aimed at: 1) evaluating the efficacy of blinatumomab in both hematologic and molecular R/R patients enrolled in clinical trials and in a real life setting; 2) identifying predictive factors impacting on overall and disease free-survival (OS and DFS), and 3) establishing the feasibility and the role of a subsequent allogenic stem cell transplantation (HSCT). Thirty-six adult patients (≥18 years) in hematologic or molecular R/R ALL were treated with blinatumomab between January 2012 and March 2017. Blinatumomab was administered either in the context of a clinical trial (Blast, MT103-211, Tower, Alcantara), in a compassionate use program or according to AIFA (Agenzia Italiana del Farmaco) guidelines. Blinatumomab was administered as continuous infusion for 4 weeks, followed by a 2-week wash out. A stepwise dose of 9 µg/day during the first week of cycle 1 followed by 28 µg/day thereafter, was administered for hematologic R/R cases and a flat dose of 15 µg /m2/day for molecular R/R patients. Patients who witnessed a response received up to 4 additional cycles or underwent a HSCT; patients showing after 1 cycle an increase in the blast count or of minimal residual disease levels, discontinued treatment. Results. Thirty-six patients were analyzed: 21 (58.4%) were in hematologic R/R and 15 (41.6%) in molecular R/R. Four patients had high-risk genetic features (2 BCR/ABL1 and 2 MLL/AF4). Thirteen patient were treated in the context of a clinical trial. All patients received at least one cycle of blinatumomab. At the end of the first cycle, among the 21 hematologic R/R pts, 14 (67%) achieved a CR and 10/14 (71%) also a CMR, while in the molecular R/R group 12/15 (80%) achieved a CMR. As expected, the rate of CMR was significantly higher in the molecular R/R cases as opposed to hematologic R/R (80% vs 52%, p=0.05). Notably, all 4 patients treated for a primary refractory disease, achieved a CR and CMR after the first cycle as opposed to hematologic relapsed cases (p=0.08). With a median follow-up of 33.9 months (range 1-89), the overall OS and DFS at 3 years are 34% and 42.5%, respectively. OS was significantly better for molecular R/R cases than for hematologic R/R cases (54.2% vs 26.1%, p=0.05), while no significant differences were observed in DFS. OS and DFS are 100%, respectively, for refractory cases. Median OS is 6.75 months for hematological R/R, while it is not reached for molecular R/R. Median DFS is 26 months for both groups. Predictive factors for non-response were the status of disease prior to blinatumomab (hematologic vs molecular R/R) and primary refractoriness. A better, though not significant, outcome was observed for patients treated in first rather than in subsequent relapse, and in cases without molecular aberrations (p=0.07, p=0.09). Overall, 14 patients - 9 with molecular and 5 with hematologic R/R at enrollment - underwent a HSCT: 8 are in continuous CR (median follow-up: 17 months, range 5-73). Among the 22 patients who did not receive a HSCT, including 16 molecular and 6 hematologic R/R at enrollment), 7 are in continuous CR (median follow-up: 51 months, range 10-89). Due to the small sample size, we cannot define the role of transplant; transplant-related mortality (TRM) was observed in 3/14 (21.4%). Treatment was well tolerated: the most common adverse events were pyrexia (55%), infectious events (33.3%) and neurotoxicity (19.4%); hematologic toxicity was rare and more frequent in hematologic R/R. Conclusions. Treatment with blinatumomab was safe and effective. As expected, patients treated in molecular R/R had better survival rates than hematologic R/R patients. Despite the small number, all primary refractory patients responded to blinatumomab, suggesting that in these cases immunotherapeutic strategies can be extremely effective, irrespective of a chemo-insensitive disease. HSCT did not impact on OS and DFS, possibly due to the small number of the cohort. Finally, no differences in terms of adverse events, DFS or OS were observed between patients treated in the context of a clinical trial or in a real-life setting. Disclosures Chiaretti: Incyte: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees. Foà:Abbvie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees.
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- 2019
45. Phase II Multicenter, Not Comparative, Study of Multiple Doses of NEPA (netupitant + palonosetron) in Preventing Chemotherapy-Induced Nausea and Vomiting (CINV) in Non-Hodgkin Lymphoma Patients Eligible for Autologous Hematopoietic Stem Cell Transplantation Receiving Multiple Days / High Dose Chemotherapy Regimens
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Giorgina Specchia, Luca Cupelli, Valentina Bozzoli, Vincenzo Federico, Patrizio Mazza, Tommasina Perrone, Clara De Risi, Nicola Di Renzo, Domenico Pastore, P Chiusolo, Maurizio Musso, Attilio Guarini, Fabio Benedetti, Giuseppe Milone, Anna Rita Messa, Vera Capria, Rosanna Scimè, and Andrea Mengarelli
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medicine.medical_specialty ,business.industry ,medicine.drug_class ,Nausea ,Immunology ,Palonosetron ,Cell Biology ,Hematology ,Biochemistry ,Chemotherapy regimen ,chemistry.chemical_compound ,Regimen ,chemistry ,Internal medicine ,Vomiting ,Netupitant ,Medicine ,Antiemetic ,medicine.symptom ,business ,Chemotherapy-induced nausea and vomiting ,medicine.drug - Abstract
Cancer chemotherapy may be associated with a high incidence of nausea and vomiting (CINV), which may occur acutely within 24 hours after the start of chemotherapy (acute phase) or in the following days (delayed phase). Despite the availability of several antiemetics, clinical findings show that control of nausea and vomiting continue to be a serious concern for hematological patients, mainly for those receiving multiple-day (MD) and high-dose (HD) chemotherapy (CT), for which no specific international recommendations have been formulated, due to the lack of a unanimous consensus between the main international guidelines. NEPA is the first antiemetic developed as an oral fixed dose combination of two drugs that are antagonists of two receptors involved in the control of nausea and vomiting: a new highly selective NK1-RA, netupitant, and a second generation 5HT3-RA, palonosetron, that simplify the antiemetic regimen allowing for a lower number of capsules and days of treatment. In clinical practice, NEPA is administered together with dexamethasone that contributes to CINV prophylaxis by its intrinsic antiemetic properties. However, dexamethasone also exhibits an important immunosuppressive activity, which could lead to several adverse events, such as increasing the risk of serious infections, especially in patients undergoing myeloablative treatment. The rational of this study was to explore the efficacy of multiple doses of NEPA given with an every-other-day regimen without dexamethasone in preventing CINV in patients with non-Hodgkin's lymphoma (NHL) eligible for autologous stem cell transplantation (ASCT) and treated with MD-HD-CT. The chemotherapy regimen (BEAM/FEAM) was administered for 6 days, NEPA was taken on day 1, 3 and 5, and nausea and vomiting were monitored up to day 15. No dexamethasone was given for antiemetic prophylaxis. The primary endpoint was the percentage of patients achieving a Complete Response (CR; no vomiting and no use of rescue medication) during the overall phase, defined as the period from day 1 (first day of chemotherapy) until 2 days after the last dose of chemotherapy. Seventy patients participated to the study. According to the adopted Fleming one-stage design, the primary endpoint of this study was achieved. Indeed, the number of complete responders for the overall phase was 60, which is greater than the predetermined cut-off of 42, representing the minimum frequency of responders for which the treatment is considered effective. In addition to the primary efficacy result, several additional endpoints were evaluated for the study period (Figure 1). The CR values were 87.1% (primary endpoint, overall phase: days 1-8), 88.6% (acute phase: days 1-6) and 98.6% (delayed phase: days 7-8), while the complete control (CR with no more than mild nausea) was 85.7% (overall phase), 88.6% (acute phase) and 95.7% (delayed phase) (Figure 1A). Moreover, the percentages of patients that did not have any emetic episodes were 88.6% (overall phase), 90% (acute phase) and 98.6% (delayed phase) and patients that did not require a rescue therapy for controlling CINV were 94.3% (overall phase), 94.3% (acute phase) and 100% (delayed phase). Daily records taken from day 1 to day 15 showed that values for all these categories were above 85% for all the days of observation (Figure 1B). Patients also documented the grade of their nausea according to the Likert scale. Moderate and severe episodes of nausea were reported by less than 10% for the overall phase and less than 5% in both acute and delayed phase and the daily values of no nausea were above 65% for each day of the treatment (Figure 1C and 1D). Indeed, the mean patient global satisfaction for the antiemetic prophylaxis for the study period was 9.13 ± 1.59 out of 10. Regarding safety, a total of 12 Treatment-Emergent Adverse Events (TEAEs) occurred in 6 (8.6%) subjects enrolled in the study. Among these, only 1 (8.3%, constipation) was evaluated as possibly related to NEPA administration. Moreover, the only two TEAEs classified as SAE (Serious Adverse Event) were two episodes of fever that have been evaluated as not-related to NEPA. Therefore, the safety profile of NEPA was confirmed also in this setting. In conclusion, our study demonstrated that multiple alternate dosing of NEPA without the addition of dexamethasone can effectively prevent nausea and vomiting in a difficult setting, such as MD/HD-CT with a good tolerability profile. Disclosures No relevant conflicts of interest to declare.
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- 2019
46. Comparative Analysis between RQ-PCR, Digital-Droplet-PCR and Next-Generation-Sequencing (NGS) of Immunoglobulin/T-Cell Receptor Gene Rearrangements to Monitor Minimal Residual Disease in Adult Acute Lymphoblastic Leukemia Patients
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Della Starza, Irene, primary, De Novi, Lucia Anna, additional, Santoro, Alessandra, additional, Domenico, Salemi, additional, Cavalli, Marzia, additional, Soscia, Roberta, additional, Paoloni, Francesca, additional, Menale, Lucia, additional, Apicella, Valerio, additional, Ilari, Caterina, additional, Vitale, Antonella, additional, Vignetti, Marco, additional, Bassan, Renato, additional, Chiaretti, Sabina, additional, Guarini, Anna, additional, and Foà, Robin, additional
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- 2018
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47. Risk of Histological Transformation in Patients with Primary Refractory Follicular Lymphoma
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Alonso, Sara, primary, Manni, Martina, additional, Sarkozy, Clementine, additional, Wondergem, Marielle, additional, Guarini, Attilio, additional, Magnano, Laura, additional, Alcoceba, Miguel, additional, Chamuleau, Martine E.D., additional, Galimberti, Sara, additional, Gomes da Silva, Maria, additional, Holte, Harald, additional, Zucca, Emanuele, additional, Montoto, Silvia, additional, Lockmer, Sandra, additional, Aurer, Igor, additional, Marcheselli, Luigi, additional, Caballero, Dolores, additional, Salles, Gilles, additional, and Federico, Massimo, additional
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- 2018
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48. Ibrutinib, Single Agent BTK Inhibitor, for Treatment Naïve (TN) and Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia: A Real-Life Experience from Rete Ematologica Pugliese (REP)
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Scalzulli, Potito Rosario, primary, Guarini, Attilio, additional, Loseto, Giacomo, additional, Specchia, Giorgina, additional, Giordano, Anna Maria, additional, Pastore, Domenico, additional, Quintana, Giovanni, additional, Mazza, Patrizio, additional, Maggi, Alessandro, additional, Di Renzo, Nicola, additional, De Paolis, Maria Rosaria, additional, Tarantini, Giuseppe, additional, De Santis, Gaetano, additional, Pavone, Vincenzo, additional, Greco, Antonino, additional, Valvano, Maria Rosa, additional, and Cascavilla, Nicola, additional
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- 2018
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49. The Combination of Complex Karyotypes' Subtypes and IGHV Mutational Status Provides Prognostic and Predictive Information in Chronic Lymphocytic Leukemia
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Visentin, Andrea, primary, Bonaldi, Laura, additional, Rigolin, Gian Matteo, additional, Mauro, Francesca Romana, additional, Martines, Annalisa, additional, Frezzato, Federica, additional, Imbergamo, Silvia, additional, Scomazzon, Edoardo, additional, Pravato, Stefano, additional, Bardi, Antonella, additional, Cavallari, Maurizio, additional, Volta, Eleonora, additional, Cavazzini, Francesco, additional, Nanni, Mauro, additional, Del Giudice, Ilaria, additional, Facco, Monica, additional, Guarini, Anna, additional, Foà, Robin, additional, Semenzato, Gianpietro, additional, Cuneo, Antonio, additional, and Trentin, Livio, additional
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- 2018
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50. TP53 Clonal and Subclonal Architecture in Chronic Lymphocytic Leukemia Patients Under Ibrutinib Treatment
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Del Giudice, Ilaria, primary, Cafforio, Luciana, additional, Cappelli, Luca Vincenzo, additional, Ilari, Caterina, additional, Raponi, Sara, additional, De Propris, Maria Stefania, additional, Mariglia, Paola, additional, Mauro, Francesca Romana, additional, Vignetti, Marco, additional, Guarini, Anna, additional, and Foà, Robin, additional
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- 2018
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