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2. Additional booster doses in patients with chronic lymphocytic leukemia induce humoral and cellular immune responses to SARS-CoV-2 similar to natural infection regardless ongoing treatments : A study by ERIC, the European Research Initiative on CLL

Author

Campanella, A., Capasso, A., Heltai, S., Taccetti, C., Albi, E., Herishanu, Y., Haggenburg, S., Chatzikonstantinou, T., Doubek, M., Kättström, Magdalena, Giannopoulos, K., Simkovic, M., Moreno, C., Massaia, M., Bumbea, H., Alshemmari, S., Ranghetti, P., Perotta, E., Martini, F., Sant'Antonio, E., Colia, M., Combi, C., Levi, S., Kater, A. P., Hazenberg, M., Nijhof, I. S., Hofsink, Q., Demosthenous, C., Kotaskova, J., Zaleska, J., Vrbacky, F., Raya, A. Mora, Bisogno, D., Tripoli, I. E., Popov, V. M., Roman, V., Stavroyianni, N., Karypidou, M., Scarano, E., Locatelli, M., Frenquelli, M., Scarfò, L., Stamatopoulos, K., Ghia, P., Campanella, A., Capasso, A., Heltai, S., Taccetti, C., Albi, E., Herishanu, Y., Haggenburg, S., Chatzikonstantinou, T., Doubek, M., Kättström, Magdalena, Giannopoulos, K., Simkovic, M., Moreno, C., Massaia, M., Bumbea, H., Alshemmari, S., Ranghetti, P., Perotta, E., Martini, F., Sant'Antonio, E., Colia, M., Combi, C., Levi, S., Kater, A. P., Hazenberg, M., Nijhof, I. S., Hofsink, Q., Demosthenous, C., Kotaskova, J., Zaleska, J., Vrbacky, F., Raya, A. Mora, Bisogno, D., Tripoli, I. E., Popov, V. M., Roman, V., Stavroyianni, N., Karypidou, M., Scarano, E., Locatelli, M., Frenquelli, M., Scarfò, L., Stamatopoulos, K., and Ghia, P.

Abstract

Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies. Booster doses increased seroconversion rate and antibody titers in all patient categories, ultimately generating humoral responses similar to those observed in the postinfection cohort. In detail, humoral response with overscale median antibody titers arose in >80% of patients in watch and wait, off-therapy in remission, or under treatment with venetoclax single-agent. Anti-CD20 antibodies and active treatment with BTK inhibitors (BTKi) represent limiting factors of humoral response, still memory mounted in ~40% of cases following booster doses or infection. (Blue) Evaluation of SARS-CoV-2-specific T-cell responses. Number of T-cell functional activation markers documented in each patient. The vast majority of patients, including those seronegative, developed T-cell responses, qualitatively similar between treatment groups or between vaccination alone and infection cases. These data highlight the efficacy of booster doses in eliciting T-cell immunity independently of treatment status and support the use of additional vaccination boosters to stimulate humoral immunity in patients on active CLL-directed treatments., The project was supported in part by Fondazione Veronesi (ID 1852164), Janssen (IBR-I-20-EMEA-014-V01/54179060CLL4024; NOPRODCLL4001), and MH CZ—DRO (FNBr, 65269705).

Published
2024
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3. Lower Patient Anxiety and Unchanged Levels of Adherence to Hemato-Oncologic Treatment in Response to New Measures to Reduce Hospital Exposure Risk to COVID-19

Author

Sarid N, Mann S, Herishanu Y, Perry C, Cohen YC, Passage I, Neaman M, Benyamini N, Jean M, and Avivi I

Subjects
anxiety, treatment adherence, covid-19, Medicine (General), R5-920
Abstract

Nadav Sarid,1,2 Shir Mann,1 Yair Herishanu,1,2 Chava Perry,1,2 Yael C Cohen,1,2 Inna Passage,1 Miriam Neaman,1,2 Noam Benyamini,1,2 Maayan Jean,1 Irit Avivi1,2 1Departments of Hematology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelCorrespondence: Irit AviviDepartment of Hematology, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, 6423906, IsraelTel +972-3-6973576Fax +972-3-6974452Email iritavi@tlvmc.gov.ilObjective: Hemato-oncology patients are at high risk for morbidity and mortality from coronavirus disease (COVID-19). The resultant heightened anxiety among these patients may negatively affect adherence to therapy and treatment-related outcome. We aimed to assess whether the adoption of precautionary measures provided by the medical team led to a reduction in COVID-19-related anxiety and, consequently, to successful execution of treatment plans.Methods: All adult hemato-oncology patients actively treated or being followed-up at the outpatient service at Tel Aviv Sourasky Medical Center between March 25 and May 3, 2020, were invited to answer a questionnaire that focused on their anxiety and adherence to treatment following new measures to reduce risk of infection during the first COVID-19 outbreak.Results: One hundred and fifty patients (representing 24% of those being approached), average age 67 years, 52% male, and 57% undergoing antineoplastic therapy, responded to the survey. The introduction of precautionary measures resulted in a significant reduction in anxiety level in all patients, irrespective of age, sex, or treatment status. Attendance to scheduled visits in day care and outpatient clinics remained unchanged. Adherence to planned blood and imaging tests were 81% and 73%, respectively, and 93% of the patients were satisfied with their medical care. Thirty-two percent of patients used telemedicine. Satisfaction with telemedicine was highest among non-actively treated patients and those experiencing high anxiety levels.Conclusion: Reorganization of the hemato-oncology unit and provision of information to patients reduced COVID-19-related anxiety and enabled the same delivery of therapy as that prior to the pandemic.Keywords: anxiety, treatment adherence, COVID-19

Published
2021

4. Additional booster doses in patients with chronic lymphocytic leukemia induce humoral and cellular immune responses to SARS‐CoV‐2 similar to natural infection regardless ongoing treatments: A study by ERIC, the European Research Initiative on CLL

Author

Campanella, A., primary, Capasso, A., additional, Heltai, S., additional, Taccetti, C., additional, Albi, E., additional, Herishanu, Y., additional, Haggenburg, S., additional, Chatzikonstantinou, T., additional, Doubek, M., additional, Kättström, M., additional, Giannopoulos, K., additional, Simkovic, M., additional, Moreno, C., additional, Massaia, M., additional, Bumbea, H., additional, Alshemmari, S., additional, Ranghetti, P., additional, Perotta, E., additional, Martini, F., additional, Sant'Antonio, E., additional, Colia, M., additional, Combi, C., additional, Levi, S., additional, Kater, A. P., additional, Hazenberg, M., additional, Nijhof, I. S., additional, Hofsink, Q., additional, Demosthenous, C., additional, Kotaskova, J., additional, Zaleska, J., additional, Vrbacky, F., additional, Raya, A. Mora, additional, Bisogno, D., additional, Tripoli, I. E., additional, Popov, V. M., additional, Roman, V., additional, Stavroyianni, N., additional, Karypidou, M., additional, Scarano, E., additional, Locatelli, M., additional, Frenquelli, M., additional, Scarfò, L., additional, Stamatopoulos, K., additional, and Ghia, P., additional

Published
2024
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7. Efficacy of front-line ibrutinib versus fludarabine, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia: A retrospective multicenter “Real-World” study

Author

Levi, S., Bronstein, Y., Goldschmidt, N., Morabito, Francesco, Ziv-Baran, T., Del Poeta, G., Bairey, O., Del Principe, M. I., Fineman, R., Mauro, F. R., Gutwein, O., Reda, G., Ruchlemer, R., Sportoletti, P., Laurenti, Luca, Shvidel, L., Coscia, M., Tadmor, T., Varettoni, M., Aviv, A., Murru, R., Braester, A., Chiarenza, A., Visentin, A., Pietrasanta, D., Loseto, G., Zucchetto, A., Bomben, R., Olivieri, J., Neri, A., Rossi, Dario, Gaidano, G., Trentin, L., Foa, Robin, Cuneo, A., Perry, C., Gattei, V., Gentile, M., Herishanu, Y., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi D., Foa R., Levi, S., Bronstein, Y., Goldschmidt, N., Morabito, Francesco, Ziv-Baran, T., Del Poeta, G., Bairey, O., Del Principe, M. I., Fineman, R., Mauro, F. R., Gutwein, O., Reda, G., Ruchlemer, R., Sportoletti, P., Laurenti, Luca, Shvidel, L., Coscia, M., Tadmor, T., Varettoni, M., Aviv, A., Murru, R., Braester, A., Chiarenza, A., Visentin, A., Pietrasanta, D., Loseto, G., Zucchetto, A., Bomben, R., Olivieri, J., Neri, A., Rossi, Dario, Gaidano, G., Trentin, L., Foa, Robin, Cuneo, A., Perry, C., Gattei, V., Gentile, M., Herishanu, Y., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi D., and Foa R.

Abstract

NA

Published
2023

8. CD84 mediates CLL-microenvironment interactions

Author

Marom, A, Barak, A F, Kramer, M P, Lewinsky, H, Binsky-Ehrenreich, I, Cohen, S, Tsitsou-Kampeli, A, Kalchenko, V, Kuznetsov, Y, Mirkin, V, Dezorella, N, Shapiro, M, Schwartzberg, P L, Cohen, Y, Shvidel, L, Haran, M, Becker-Herman, S, Herishanu, Y, and Shachar, I

Published
2017
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9. P666: ACALABRUTINIB ± OBINUTUZUMAB VS OBINUTUZUMAB + CHLORAMBUCIL IN TREATMENT-NAIVE CHRONIC LYMPHOCYTIC LEUKEMIA: 5-YEAR FOLLOW-UP OF ELEVATE-TN

Author

Sharman, J. P., primary, Egyed, M., additional, Jurczak, W., additional, Skarbnik, A., additional, Patel, K., additional, Flinn, I. W., additional, Kamdar, M., additional, Munir, T., additional, Walewska, R., additional, Fogliatto, L. M., additional, Herishanu, Y., additional, Banerji, V., additional, Follows, G., additional, Walker, P., additional, Karlsson, K., additional, Ghia, P., additional, Janssens, A., additional, Cymbalista, F., additional, Ferrant, E., additional, Wierda, W. G., additional, Munugalavadla, V., additional, Yu, T., additional, Wang, M. H., additional, and Woyach, J. A., additional

Published
2022
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10. P1086: FAVEZELIMAB (ANTI–LAG-3) AND PEMBROLIZUMAB CO-BLOCKADE IN ANTI–PD-1–NAIVE PATIENTS WITH RELAPSED OR REFRACTORY CLASSICAL HODGKIN LYMPHOMA: AN OPEN-LABEL PHASE 1/2 STUDY

Author

Gregory, G., primary, Timmerman, J., additional, Lavie, D., additional, Borchmann, P., additional, Herrera, A. F., additional, Minuk, L., additional, Vucinic, V., additional, Armand, P., additional, Avigdor, A., additional, Gasiorowski, R., additional, Herishanu, Y., additional, Keane, C., additional, Kuruvilla, J., additional, Palcza, J., additional, Pillai, P., additional, Marinello, P., additional, and Johnson, N. A., additional

Published
2022
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11. Favezelimab (anti-LAG-3) plus pembrolizumab in patients with anti-PD-1-naive relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL): An open-label phase 1/2 study.

Author

Johnson N.A., Lavie D., Borchmann P., Gregory G., Herrera A.F., Minuk L., Vucinic V., Armand P., Avigdor A., Gasiorowski R., Herishanu Y., Keane C., Kuruvilla J., Palcza J., Pillai P., Marinello P., Timmerman J., Johnson N.A., Lavie D., Borchmann P., Gregory G., Herrera A.F., Minuk L., Vucinic V., Armand P., Avigdor A., Gasiorowski R., Herishanu Y., Keane C., Kuruvilla J., Palcza J., Pillai P., Marinello P., and Timmerman J.

Abstract

Background: PD-1 inhibitors are a standard of care in pts with R/R cHL but new approaches are still needed to deepen and lengthen responses. Dual blockade of PD-1 and LAG-3 has demonstrated antitumor activity in preclinical models. The multicohort phase 1/2 MK-4280-003 study (NCT03598608) evaluated the safety and efficacy of favezelimab (MK-4280), a humanized IgG4 LAG-3 inhibitor, plus pembrolizumab (pembro; a PD-1 inhibitor) in pts with R/R hematologic malignancies. This analysis focused on anti-PD-1-naive pts with R/R cHL (cohort 1). Method(s): This study included a safety lead-in phase (part 1) to determine the recommended phase 2 dose (RP2D) followed by a dose-expansion phase (part 2). Eligible pts in cohort 1 must have R/R cHL after autologous stem cell transplantation (ASCT) or be ineligible for ASCT and have had no prior anti-PD-1 therapy. In part 1, patients from all cohorts received pembro IV 200 mg Q3W and favezelimab IV 200 mg or 800 mg Q3W. Dose escalation followed the mTPI design. In part 2, pts received pembro + favezelimab at the established RP2D for up to 35 cycles. Primary end point was safety. Secondary end point was ORR. DOR, PFS, and OS were exploratory end points. Result(s): Only 1 dose-limiting toxicity (DLT; autoimmune hepatitis [grade 4]) was identified among the first 6 pts from all cohorts in part 1 at the favezelimab 200 mg dose; thus, the dose was escalated to 800 mg. No DLTs were observed in the 15 additional pts treated at the 800 mg dose. The RP2D for the combination was defined as 800 mg Q3W + pembro 200 mg Q3W. In cohort 1, 30 pts were enrolled; median age was 40 years, 53% had ECOG PS 0, and 80% had <=3 prior lines of therapy. After a median follow-up of 13.5 mo, ORR for cohort 1 was 73% (95% CI, 54-88; CR, 7 pts [23%]; PR, 15 pts [50%]). 28 of 30 pts (93%) had reduction from baseline in target lesions. Median DOR was not reached (NR; 95% CI, 0+ to 23+ mo); 6 pts (51%) had response >=12 mo. Median PFS was 19 mo (95% CI, 8-NR); 12-mo

Published
2022

12. Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

Author

Antic, D., Milic, N., Chatzikonstantinou, T., Scarfo, L., Otasevic, V., Rajovic, N., Allsup, D., Alonso Cabrero, A., Andres, M., Baile Gonzales, M., Capasso, A., Collado, R., Cordoba, R., Cuellar-Garcia, C., Correa, J. G., De Paoli, L., De Paolis, M. R., Del Poeta, G., Dimou, M., Doubek, M., Efstathopoulou, M., El-Ashwah, S., Enrico, A., Espinet, B., Farina, L., Ferrari, A., Foglietta, M., Lopez-Garcia, A., Garcia-Marco, J. A., Garcia-Serra, R., Gentile, Marino, Gimeno, E., da Silva, M. G., Gutwein, O., Hakobyan, Y. K., Herishanu, Y., Hernandez-Rivas, J. A., Herold, T., Itchaki, G., Jaksic, O., Janssens, A., Kalashnikova, O. B., Kalicinska, E., Kater, A. P., Kersting, S., Koren-Michowitz, M., Labrador, J., Lad, D., Laurenti, Luca, Fresa, Alberto, Levin, M. -D., Mayor Bastida, C., Malerba, L., Marasca, R., Marchetti, M., Marquet, J., Mihaljevic, B., Milosevic, I., Miras, F., Morawska, M., Motta, M., Munir, T., Murru, R., Nunes, R., Olivieri, J., Pavlovsky, M. A., Piskunova, I., Popov, V. M., Quaglia, F. M., Quaresmini, G., Reda, G., Rigolin, G. M., Shrestha, A., Simkovic, M., Smirnova, S., Spacek, M., Sportoletti, P., Stanca, O., Stavroyianni, N., Te Raa, D., Tomic, K., Tonino, S., Trentin, L., Van Der Spek, E., van Gelder, M., Varettoni, M., Visentin, A., Vitale, C., Vukovic, Vladimir, Wasik-Szczepanek, E., Wrobel, T., Segundo, L. Y. S., Yassin, M., Coscia, M., Rambaldi, A., Montserrat, E., Foa, Robin, Cuneo, A., Carrier, M., Ghia, P., Stamatopoulos, K., Gentile M., Laurenti L. (ORCID:0000-0002-8327-1396), Fresa A., Vukovic V. (ORCID:0000-0002-9561-7825), Foa R., Antic, D., Milic, N., Chatzikonstantinou, T., Scarfo, L., Otasevic, V., Rajovic, N., Allsup, D., Alonso Cabrero, A., Andres, M., Baile Gonzales, M., Capasso, A., Collado, R., Cordoba, R., Cuellar-Garcia, C., Correa, J. G., De Paoli, L., De Paolis, M. R., Del Poeta, G., Dimou, M., Doubek, M., Efstathopoulou, M., El-Ashwah, S., Enrico, A., Espinet, B., Farina, L., Ferrari, A., Foglietta, M., Lopez-Garcia, A., Garcia-Marco, J. A., Garcia-Serra, R., Gentile, Marino, Gimeno, E., da Silva, M. G., Gutwein, O., Hakobyan, Y. K., Herishanu, Y., Hernandez-Rivas, J. A., Herold, T., Itchaki, G., Jaksic, O., Janssens, A., Kalashnikova, O. B., Kalicinska, E., Kater, A. P., Kersting, S., Koren-Michowitz, M., Labrador, J., Lad, D., Laurenti, Luca, Fresa, Alberto, Levin, M. -D., Mayor Bastida, C., Malerba, L., Marasca, R., Marchetti, M., Marquet, J., Mihaljevic, B., Milosevic, I., Miras, F., Morawska, M., Motta, M., Munir, T., Murru, R., Nunes, R., Olivieri, J., Pavlovsky, M. A., Piskunova, I., Popov, V. M., Quaglia, F. M., Quaresmini, G., Reda, G., Rigolin, G. M., Shrestha, A., Simkovic, M., Smirnova, S., Spacek, M., Sportoletti, P., Stanca, O., Stavroyianni, N., Te Raa, D., Tomic, K., Tonino, S., Trentin, L., Van Der Spek, E., van Gelder, M., Varettoni, M., Visentin, A., Vitale, C., Vukovic, Vladimir, Wasik-Szczepanek, E., Wrobel, T., Segundo, L. Y. S., Yassin, M., Coscia, M., Rambaldi, A., Montserrat, E., Foa, Robin, Cuneo, A., Carrier, M., Ghia, P., Stamatopoulos, K., Gentile M., Laurenti L. (ORCID:0000-0002-8327-1396), Fresa A., Vukovic V. (ORCID:0000-0002-9561-7825), and Foa R.

Abstract

Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occu

Published
2022

13. Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

Author

Antic D, Milic N, Chatzikonstantinou T, Scarfò L, Otasevic V, Rajovic N, Allsup D, Alonso Cabrero A, Andres M, Baile Gonzales M, Capasso A, Collado R, Cordoba R, Cuéllar-García C, Correa JG, De Paoli L, De Paolis MR, Del Poeta G, Dimou M, Doubek M, Efstathopoulou M, El-Ashwah S, Enrico A, Espinet B, Farina L, Ferrari A, Foglietta M, Lopez-Garcia A, García-Marco JA, García-Serra R, Gentile M, Gimeno E, da Silva MG, Gutwein O, Hakobyan YK, Herishanu Y, Hernández-Rivas JÁ, Herold T, Itchaki G, Jaksic O, Janssens A, Kalashnikova OB, Kalicińska E, Kater AP, Kersting S, Koren- Michowitz M, Labrador J, Lad D, Laurenti L, Fresa A, Levin MD, Mayor Bastida C, Malerba L, Marasca R, Marchetti M, Marquet J, Mihaljevic B, Milosevic I, Mirás F, Morawska M, Motta M, Munir T, Murru R, Nunes R, Olivieri J, Pavlovsky MA, Piskunova I, Popov VM, Quaglia FM, Quaresmini G, Reda G, Rigolin GM, Shrestha A, Šimkovič M, Smirnova S, Špaček M, Sportoletti P, Stanca O, Stavroyianni N, Te Raa D, Tomic K, Tonino S, Trentin L, Van Der Spek E, van Gelder M, Varettoni M, Visentin A, Vitale C, Vukovic V, Wasik-Szczepanek E, Wróbel T, Segundo LYS, Yassin M, Coscia M, Rambaldi A, Montserrat E, Foà R, Cuneo A, Carrier M, Ghia P, Stamatopoulos K.

Subjects
Age, Anticoagulation therapy, Bleeding, CLL, COVID-19, D-dimer, LMWH, Thromboprophylaxis, Thrombosis
Abstract

Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment- related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS- CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C- reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017-1.109 and OR = 2.438, 95%CI 1.023-5.813, respectively). Conclusions: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

Published
2022

16. An open‐label phase 1/2 study of favezelimab plus pembrolizumab in patients with relapsed/refractory classical Hodgkin lymphoma with/without previous anti‐PD‐1 treatment.

Author

Lavie, D., Johnson, N., Borchmann, P., Herrera, A. F., Avigdor, A., Gasiorowski, R., Gregory, G., Keane, C., Vucinic, V., Bazargan, M., Herishanu, Y., Minuk, L., Tzoran, I., Andreadis, C., Armand, P., Kuruvilla, J., Zinzani, P. L., West, R. Marceau, Pillai, P., and Marinello, P.

Subjects
HODGKIN'S disease, PEMBROLIZUMAB
Abstract

B Introduction: b Dual blockade of PD-1 and lymphocyte-activation gene (LAG-3) has shown antitumor activity; however, the activity of the combination for patients (pts) with relapsed or refractory (R/R) classical Hodgkin's lymphoma (cHL) is unclear. An open-label phase 1/2 study of favezelimab plus pembrolizumab in patients with relapsed/refractory classical Hodgkin lymphoma with/without previous anti-PD-1 treatment Pts in cohort 1 had no prior anti-PD-1 therapy; pts in cohort 2 had progression within 12 weeks after >=2 doses of anti-PD-1 therapy, per Cheson 2007 criteria. [Extracted from the article]

Published
2023
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17. Effectiveness of ibrutinib as first-line therapy for chronic lymphocytic leukemia patients and indirect comparison with rituximab-bendamustine: Results of study on 486 cases outside clinical trials

Author

Morabito, F., Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, L., Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, F. M., Zucchetto, A., Al-Janazreh, H., Vigna, E., Martino, E. A., Cassin, R., D'Arrigo, G., Galimberti, S., Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Monti, P., Menichini, P., Olivieri, J., Cutrona, G., Rossi, D., Cuneo, A., Di Raimondo, F., Gaidano, G., Polliack, A., Trentin, L., Foa, R., Ferrarini, M., Gattei, V., Gentile, M., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Monti P. (ORCID:0000-0002-2586-1881), Rossi D., Foa R., Gentile M., Morabito, F., Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, L., Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, F. M., Zucchetto, A., Al-Janazreh, H., Vigna, E., Martino, E. A., Cassin, R., D'Arrigo, G., Galimberti, S., Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Monti, P., Menichini, P., Olivieri, J., Cutrona, G., Rossi, D., Cuneo, A., Di Raimondo, F., Gaidano, G., Polliack, A., Trentin, L., Foa, R., Ferrarini, M., Gattei, V., Gentile, M., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Monti P. (ORCID:0000-0002-2586-1881), Rossi D., Foa R., and Gentile M.

Abstract

n/a

Published
2021

18. Comparison of ibrutinib and idelalisib plus rituximab in real-life relapsed/resistant chronic lymphocytic leukemia cases

Author

Morabito, Francesco, Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Vigna, E., Martino, E. A., Mendicino, F., Cassin, R., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Monti, Paolo, Menichini, P., Cutrona, G., Jaksic, O., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Monti P. (ORCID:0000-0002-2586-1881), Rossi D., Foa R., Gentile M., Morabito, Francesco, Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Vigna, E., Martino, E. A., Mendicino, F., Cassin, R., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Monti, Paolo, Menichini, P., Cutrona, G., Jaksic, O., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Monti P. (ORCID:0000-0002-2586-1881), Rossi D., Foa R., and Gentile M.

Abstract

Objectives: To compare the capacity of ibrutinib (IB) and idelalisib-rituximab (IDELA-R) of prolonging overall survival (OS) as in CLL patients, previously treated with chemotherapy only. Methods: A real-life cohort of 675 cases has been identified and investigated in the database of the groups participating in the study. Results: At an unadjusted univariate analysis, a significant death risk reduction was observed favoring IB (IDELA-R vs IB HR = 0.5, 95% CI = 0.36-0.71) although with some limitations due to the non-randomized and retrospective nature of the study and to the lower number of patients in the IDELA-R group (112 cases) related to the current prescribing practice. To overcome the potential problem of confounding by indication, we adjusted the association between the type of therapy and mortality for all variables significantly associated with OS at Cox univariate analysis. Furthermore, those variables, differently distributed between the two study groups, were introduced into the multivariate Cox model to improve the effectiveness of the analysis. By introducing all these variables into the multiple Cox regression model, we confirmed the protective effect of IB vs IDELA-R (HR = 0.67, 95% CI = 0.45-0.98, P =.04) independent of potential confounders. Conclusions: Although our analysis presents some constraints, that is, the unavailability of additional potential confounders, and the retrospective nature of the study, this observation may be of help for the daily clinical practice, particularly in the absence of randomized trials comparing the two schedules.

Published
2021

19. Assessment of the 4-factor score: Retrospective analysis of 586 CLL patients receiving ibrutinib. A campus CLL study

Author

Morabito, Francesco, Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Vigna, E., Martino, E. A., Mendicino, F., Botta, C., Caracciolo, D., Cassin, R., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Cutrona, G., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Rossi D., Foa R., Gentile M., Morabito, Francesco, Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Vigna, E., Martino, E. A., Mendicino, F., Botta, C., Caracciolo, D., Cassin, R., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Cutrona, G., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Rossi D., Foa R., and Gentile M.

Abstract

n/a

Published
2021

20. Survival risk score for real-life relapsed/refractory chronic lymphocytic leukemia patients receiving ibrutinib. A campus CLL study

Author

Gentile, Marino, Morabito, Francesco, Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Recchia, A. G., Varettoni, M., Murru, R., Chiarenza, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Fraticelli, V., Vigna, E., Botta, C., Tripepi, G., Arrigo, G. D., Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Rigolin, G. M., Rossi, Dario, Di Raimondo, F., Gaidano, G., Polliack, A., Cuneo, A., Foa, Robin, Gattei, V., Gentile M., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Rossi D., Foa R., Gentile, Marino, Morabito, Francesco, Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Recchia, A. G., Varettoni, M., Murru, R., Chiarenza, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Fraticelli, V., Vigna, E., Botta, C., Tripepi, G., Arrigo, G. D., Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Rigolin, G. M., Rossi, Dario, Di Raimondo, F., Gaidano, G., Polliack, A., Cuneo, A., Foa, Robin, Gattei, V., Gentile M., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Rossi D., and Foa R.

Abstract

N/A

Published
2021

21. Frontline treatment with the combination obinutuzumab±chlorambucil for chronic lymphocytic leukemia outside clinical trials: results of a multinational, multicenter study by ERIC and the Israeli CLL study group

Author

Herishanu Y, Shaulov A, Fineman R, BasiC-Kinda S, Aviv A, Wasik-Szczepanek E, Jaksic O, Zdrenghea M, Greenbaum U, Mandac I, Simkovic M, Morawska M, Benjamini O, Spacek M, Nemets A, Bairey O, Trentin L, Ruchlemer R, Laurenti L, Ciocan O, Doubek M, Shvidel L, Dali N, Miras F, De Meuter A, Dimou M, Mauro F, Coscia M, Bumbea H, Szasz R, Tadmor T, Gutwein O, Gentile M, Scarfo L, Tedeschi A, Sportoletti P, Vazquez E, Marquet J, Assouline S, Papaioannou M, Braester A, Levato L, Gregor M, Rigolin G, Loscertales J, Perez A, Nijziel M, Popov V, Collado R, Slavutsky I, Itchaki G, Ringelstein S, Goldschmidt N, Perry C, Levi S, Polliack A, and Ghia P

Abstract

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O±Clb in unfit patients with CLL, in a "real-world" setting. Patients with documented del(17p13.1)/TP53mutation were excluded. A total of 437 patients (median age, 75.9years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min)were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95%CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del(11q22.3) and/or IGHV-unmutated], lymph nodes of diameter >5cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a "real-world" setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del(11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease. This article is protected by copyright. All rights reserved.

Published
2020

22. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus

Author

Scarfo, L, Chatzikonstantinou, T, Rigolin, GM, Quaresmini, G, Motta, M, Vitale, C, Garcia-Marco, JA, Hernandez-Rivas, JA, Miras, F, Baile, M, Marquet, J, Niemann, CU, Reda, G, Munir, T, Gimeno, E, Marchetti, M, Quaglia, FM, Varettoni, M, Delgado, J, Iyengar, S, Janssens, A, Marasca, R, Ferrari, A, Cuellar-Garcia, C, Itchaki, G, Spacek, M, De Paoli, L, Laurenti, L, Levin, M-D, Lista, E, Mauro, FR, Simkovic, M, Van Der Spek, E, Vandenberghe, E, Trentin, L, Wasik-Szczepanek, E, Ruchlemer, R, Bron, D, De Paolis, MR, Del Poeta, G, Farina, L, Foglietta, M, Gentile, M, Herishanu, Y, Herold, T, Jaksic, O, Kater, AP, Kersting, S, Malerba, L, Orsucci, L, Popov, VM, Sportoletti, P, Yassin, M, Pocali, B, Barna, G, Chiarenza, A, dos Santos, G, Nikitin, E, Andres, M, Dimou, M, Doubek, M, Enrico, A, Hakobyan, Y, Kalashnikova, O, Ortiz Pareja, M, Papaioannou, M, Rossi, D, Shah, N, Shrestha, A, Stanca, O, Stavroyianni, N, Strugov, V, Tam, C, Zdrenghea, M, Coscia, M, Stamatopoulos, K, Rossi, G, Rambaldi, A, Montserrat, E, Foa, R, Cuneo, A, Ghia, P, Scarfo, L, Chatzikonstantinou, T, Rigolin, GM, Quaresmini, G, Motta, M, Vitale, C, Garcia-Marco, JA, Hernandez-Rivas, JA, Miras, F, Baile, M, Marquet, J, Niemann, CU, Reda, G, Munir, T, Gimeno, E, Marchetti, M, Quaglia, FM, Varettoni, M, Delgado, J, Iyengar, S, Janssens, A, Marasca, R, Ferrari, A, Cuellar-Garcia, C, Itchaki, G, Spacek, M, De Paoli, L, Laurenti, L, Levin, M-D, Lista, E, Mauro, FR, Simkovic, M, Van Der Spek, E, Vandenberghe, E, Trentin, L, Wasik-Szczepanek, E, Ruchlemer, R, Bron, D, De Paolis, MR, Del Poeta, G, Farina, L, Foglietta, M, Gentile, M, Herishanu, Y, Herold, T, Jaksic, O, Kater, AP, Kersting, S, Malerba, L, Orsucci, L, Popov, VM, Sportoletti, P, Yassin, M, Pocali, B, Barna, G, Chiarenza, A, dos Santos, G, Nikitin, E, Andres, M, Dimou, M, Doubek, M, Enrico, A, Hakobyan, Y, Kalashnikova, O, Ortiz Pareja, M, Papaioannou, M, Rossi, D, Shah, N, Shrestha, A, Stanca, O, Stavroyianni, N, Strugov, V, Tam, C, Zdrenghea, M, Coscia, M, Stamatopoulos, K, Rossi, G, Rambaldi, A, Montserrat, E, Foa, R, Cuneo, A, and Ghia, P

Abstract

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79–7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.

Published
2020

23. Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group

Author

Herishanu, Y., Shaulov, A., Fineman, R., Basic-Kinda, S., Aviv, A., Wasik-Szczepanek, E., Jaksic, O., Zdrenghea, M., Greenbaum, U., Mandac, I., Simkovic, M., Morawska, M., Benjamini, O., Spacek, M., Nemets, A., Bairey, O., Trentin, L., Ruchlemer, R., Laurenti, Luca, Stanca Ciocan, O., Doubek, M., Shvidel, L., Dali, N., Miras, F., De Meuter, A., Dimou, M., Mauro, F. R., Coscia, M., Bumbea, H., Szasz, R., Tadmor, T., Gutwein, O., Gentile, Marino, Scarfo, L., Tedeschi, Alessandra, Sportoletti, P., Gimeno Vazquez, E., Marquet, J., Assouline, S., Papaioannou, M., Braester, A., Levato, L., Gregor, M., Rigolin, G. M., Loscertales, J., Medina Perez, A., Nijziel, M. R., Popov, V. M., Collado, R., Slavutsky, I., Itchaki, G., Ringelstein, S., Goldschmidt, N., Perry, C., Levi, S., Polliack, A., Ghia, P., Laurenti L. (ORCID:0000-0002-8327-1396), Gentile M., Tedeschi A., Herishanu, Y., Shaulov, A., Fineman, R., Basic-Kinda, S., Aviv, A., Wasik-Szczepanek, E., Jaksic, O., Zdrenghea, M., Greenbaum, U., Mandac, I., Simkovic, M., Morawska, M., Benjamini, O., Spacek, M., Nemets, A., Bairey, O., Trentin, L., Ruchlemer, R., Laurenti, Luca, Stanca Ciocan, O., Doubek, M., Shvidel, L., Dali, N., Miras, F., De Meuter, A., Dimou, M., Mauro, F. R., Coscia, M., Bumbea, H., Szasz, R., Tadmor, T., Gutwein, O., Gentile, Marino, Scarfo, L., Tedeschi, Alessandra, Sportoletti, P., Gimeno Vazquez, E., Marquet, J., Assouline, S., Papaioannou, M., Braester, A., Levato, L., Gregor, M., Rigolin, G. M., Loscertales, J., Medina Perez, A., Nijziel, M. R., Popov, V. M., Collado, R., Slavutsky, I., Itchaki, G., Ringelstein, S., Goldschmidt, N., Perry, C., Levi, S., Polliack, A., Ghia, P., Laurenti L. (ORCID:0000-0002-8327-1396), Gentile M., and Tedeschi A.

Abstract

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O ± Clb in unfit patients with CLL, in a “real-world” setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a “real-world” setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.

Published
2020

24. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus

Author

Scarfo, L., Chatzikonstantinou, T., Rigolin, G. M., Quaresmini, G., Motta, M., Vitale, C., Garcia-Marco, J. A., Hernandez-Rivas, J. A., Miras, F., Baile, M., Marquet, J., Niemann, C. U., Reda, G., Munir, T., Gimeno, E., Marchetti, M., Quaglia, F. M., Varettoni, M., Delgado, J., Iyengar, S., Janssens, A., Marasca, R., Ferrari, A., Cuellar-Garcia, C., Itchaki, G., Spacek, M., De Paoli, L., Laurenti, Luca, Levin, M. -D., Lista, E., Mauro, F. R., Simkovic, M., Van Der Spek, E., Vandenberghe, E., Trentin, L., Wasik-Szczepanek, E., Ruchlemer, R., Bron, D., De Paolis, M. R., Del Poeta, G., Farina, L., Foglietta, M., Gentile, Marino, Herishanu, Y., Herold, T., Jaksic, O., Kater, A. P., Kersting, S., Malerba, L., Orsucci, L., Popov, V. M., Sportoletti, P., Yassin, M., Pocali, B., Barna, G., Chiarenza, A., dos Santos, G., Nikitin, E., Andres, M., Dimou, M., Doubek, M., Enrico, A., Hakobyan, Y., Kalashnikova, O., Ortiz Pareja, M., Papaioannou, M., Rossi, Dario, Shah, N., Shrestha, A., Stanca, O., Stavroyianni, N., Strugov, V., Tam, C., Zdrenghea, M., Coscia, M., Stamatopoulos, K., Rossi, G., Rambaldi, A., Montserrat, E., Foa, Robin, Cuneo, A., Ghia, P., Laurenti L. (ORCID:0000-0002-8327-1396), Gentile M., Rossi D., Foa R., Scarfo, L., Chatzikonstantinou, T., Rigolin, G. M., Quaresmini, G., Motta, M., Vitale, C., Garcia-Marco, J. A., Hernandez-Rivas, J. A., Miras, F., Baile, M., Marquet, J., Niemann, C. U., Reda, G., Munir, T., Gimeno, E., Marchetti, M., Quaglia, F. M., Varettoni, M., Delgado, J., Iyengar, S., Janssens, A., Marasca, R., Ferrari, A., Cuellar-Garcia, C., Itchaki, G., Spacek, M., De Paoli, L., Laurenti, Luca, Levin, M. -D., Lista, E., Mauro, F. R., Simkovic, M., Van Der Spek, E., Vandenberghe, E., Trentin, L., Wasik-Szczepanek, E., Ruchlemer, R., Bron, D., De Paolis, M. R., Del Poeta, G., Farina, L., Foglietta, M., Gentile, Marino, Herishanu, Y., Herold, T., Jaksic, O., Kater, A. P., Kersting, S., Malerba, L., Orsucci, L., Popov, V. M., Sportoletti, P., Yassin, M., Pocali, B., Barna, G., Chiarenza, A., dos Santos, G., Nikitin, E., Andres, M., Dimou, M., Doubek, M., Enrico, A., Hakobyan, Y., Kalashnikova, O., Ortiz Pareja, M., Papaioannou, M., Rossi, Dario, Shah, N., Shrestha, A., Stanca, O., Stavroyianni, N., Strugov, V., Tam, C., Zdrenghea, M., Coscia, M., Stamatopoulos, K., Rossi, G., Rambaldi, A., Montserrat, E., Foa, Robin, Cuneo, A., Ghia, P., Laurenti L. (ORCID:0000-0002-8327-1396), Gentile M., Rossi D., and Foa R.

Abstract

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79–7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.

Published
2020

29. TP53 disruption as a risk factor in the era of targeted therapies: A multicenter retrospective study of 525 chronic lymphocytic leukemia cases

Author

Morabito, Francesco, Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Recchia, A. G., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Martino, E. A., Vigna, E., Tripepi, G., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Cutrona, G., Jaksic, O., Olivieri, J., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Rossi D., Foa R., Gentile M., Morabito, Francesco, Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Recchia, A. G., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Martino, E. A., Vigna, E., Tripepi, G., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Cutrona, G., Jaksic, O., Olivieri, J., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Rossi D., Foa R., and Gentile M.

Abstract

n/a

Published
2019

36. Clustering of Parkinson's disease points to environmental etiology

Author

Goldsmith, J.R., Herishanu, Y., Abarbanel, J.M., and Weinbaum, Z.

Subjects
Parkinsonism -- Environmental aspects, Parkinsonism -- Demographic aspects, Parkinsonism -- Causes of, Environmental issues, Health
Abstract

Thirteen cases of Parkinson's disease, a degenerative disease of the nervous system, developed among the residents of three kibbutzim in southern Israel, which reflects a five times greater incidence than observed in the surrounding region. Parkinson's disease has many suggested causes, but in all cases the symptoms are the same. These clusters found in Israel suggest a common environmental causative factor such as the drinking water, since these three kibbutzim have used the same aquifer for many years. The source of ground water contamination may be a waste disposal site located near one kibbutz. When the water was examined and compared with other sources, a high level of aluminum was found, along with smaller excess quantities of iron and manganese. The local soil contained excess concentrations of beryllium, chromium, europium, manganese, and ytterbium. Two of the commonly used agricultural chemicals in the region, Maneb (which contains manganese) and Paraquat, have been associated with Parkinsonism in the past. Further measurement and study of local water and air contaminants are needed to clarify the cause of these cases of Parkinson's disease, and to prevent additional cases from developing. (Consumer Summary produced by Reliance Medical Information, Inc.), Clustering of Parkinson's Disease Points to Environmental Etiology PARKINSON'S DISEASE is a common, slowly progressive affliction of older persons, for which, despite several known causes, there is no general etiology. [...]

Published
1990

37. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS) : a randomised, double-blind, phase 3 study

Author

Chanan-Khan, Asher, Cramer, Paula, Demirkan, Fatih, Fraser, Graeme, Silva, Rodrigo Santucci, Grosicki, Sebastian, Pristupa, Aleksander, Janssens, Ann, Mayer, Jiri, Bartlett, Nancy L, Dilhuydy, Marie-Sarah, Pylypenko, Halyna, Loscertales, Javier, Avigdor, Abraham, Rule, Simon, Villa, Diego, Samoilova, Olga, Panagiotidis, Panagiots, Goy, Andre, Mato, Anthony, Pavlovsky, Miguel A, Karlsson, Claes, Mahler, Michelle, Salman, Mariya, Sun, Steven, Phelps, Charles, Balasubramanian, Sriram, Howes, Angela, Hallek, Michael, Assouline, S, Bence-Bruckler, I, Buckstein, R, Fraser, G, Larratt, L, Minuk, L, Villa, D, Angevine, A, Bartlett, N, Bixby, D, Caimi, P, Chanan-Khan, A, Craig, M, Forero-Torres, A, Ganguly, S, Goy, A, Heffner, L, Hermann, R, Lansigan, F, Leis, J, Letzer, J, Link, B, Liu, D, McCaul, K, McGuire, E, Skinner, W, Starodub, A, Stuart, R, Thirman, M, Tirumali, N, Yang, J, Janssens, A, Offner, F, Van den Neste, E, Van Hoof, A, Mayer, J, Novak, J, Trneny, M, Cartron, G, Dartigeas, C, Dilhuydy, M, Ghez, D, Haioun, C, Leblond, V, Salles, G, Balser, C, Cramer, P, Dreger, P, Durig, J, Eckart, M, Heinrich, B, Illmer, T, Jentsch-Ullrich, K, Pfreundschuh, M, Schetelig, J, Schlag, R, Soling, U, Stilgenbauer, S, Anagnostopoulos, A, Dimopoulos, A, Panagiotidis, P, Vrakidou, E, Bairey, O, Yehuda, D Ben, Braester, A, Fineman, R, Herishanu, Y, Nagler, A, Ruchlemer, R, Tadmor, T, Grosicki, S, Homenda, W, Jurczak, W, Pluta, A, Woszczyk, D, Espirito Santo, A, Luis, R, Raposo, J, Viveiros, C, Alexeeva, J, Dunaev, Y, Golubeva, M, Khuageva, N, Loginov, A, Lysenko, I, Osmanov, E, Pavlov, V, Pristupa, A, Proydakov, A, Rossiev, V, Samarina, I, Samoilova, O, Serduk, O, Shneider, T, Udovitsa, D, Voloshin, S, Gayoso, J, Gonzalez, M, Gonzalez Barca, E, Hernandez Rivas, J, Jargue, I, Loscertales, J, Karlsson, C, Sender, M, Aktan, M, Arslan, O, Demirkan, F, Ferhanoglu, B, Kaynar, L, Sayinalp, N, Vaural, F, Yagci, M, Dyagil, I, Kaplan, P, Masliak, Z, Oliynyk, H, Popovska, T, Pylypenko, H, Rekhtman, G, Dearden, C, Morley, N, Moss, P, Rule, S, Pavlovsky, M, Riveros, D, Santucci-Silva, R, Romeo, M, Scheliga, A, Salazar, L, Gomez, D, Ramirez, E, and Jung, C

Subjects
Male, Medizin, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Atrial Fibrillation, Bendamustine Hydrochloride, Aged, 80 and over, Anemia, Nausea, Middle Aged, 3. Good health, Fludarabine, Intention to Treat Analysis, Oncology, 030220 oncology & carcinogenesis, Ibrutinib, Retreatment, Disease Progression, Rituximab, Female, medicine.drug, Bendamustine, Adult, medicine.medical_specialty, Neutropenia, Hemorrhage, Disease-Free Survival, 03 medical and health sciences, Double-Blind Method, Internal medicine, medicine, Humans, Aged, Performance status, business.industry, Adenine, medicine.disease, Interim analysis, Leukemia, Lymphocytic, Chronic, B-Cell, Thrombocytopenia, Surgery, Regimen, Pyrimidines, chemistry, Pyrazoles, Mantle cell lymphoma, business, 030215 immunology
Abstract

Most patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma relapse after initial therapy. Bendamustine plus rituximab is often used in the relapsed or refractory setting. We assessed the efficacy and safety of adding ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK), to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma.The HELIOS trial was an international, double-blind, placebo-controlled, phase 3 study in adult patients (≥18 years of age) who had active chronic lymphocytic leukaemia or small lymphocytic lymphoma with measurable lymph node disease (1·5 cm) by CT scan, and had relapsed or refractory disease following one or more previous lines of systemic therapy consisting of at least two cycles of a chemotherapy-containing regimen, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate bone marrow, liver, and kidney function. Patients with del(17p) were excluded because of known poor response to bendamustine plus rituximab. Patients who had received previous treatment with ibrutinib or other BTK inhibitors, refractory disease or relapse within 24 months with a previous bendamustine-containing regimen, or haemopoietic stem-cell transplant were also excluded. Patients were randomly assigned (1:1) by a web-based system to receive bendamustine plus rituximab given in cycles of 4 weeks' duration (bendamustine: 70 mg/m(2) intravenously on days 2-3 in cycle 1, and days 1-2 in cycles 2-6; rituximab: 375 mg/m(2) on day 1 of cycle 1, and 500 mg/m(2) on day 1 of cycles 2-6 for a maximum of six cycles) with either ibrutinib (420 mg daily orally) or placebo until disease progression or unacceptable toxicity. Patients were stratified according to whether they were refractory to purine analogues and by number of previous lines of therapy. The primary endpoint was independent review committee (IRC)-assessed progression-free survival. Crossover to ibrutinib was permitted for patients in the placebo group with IRC-confirmed disease progression. Analysis was by intention-to-treat and is continuing for further long-term follow-up. The trial is registered with ClinicalTrials.gov, number NCT01611090.Between Sept 19, 2012, and Jan 21, 2014, 578 eligible patients were randomly assigned to ibrutinib or placebo in combination with bendamustine plus rituximab (289 in each group). The primary endpoint was met at the preplanned interim analysis (March 10, 2015). At a median follow-up of 17 months (IQR 13·7-20·7), progression-free survival was significantly improved in the ibrutinib group compared with the placebo group (not reached in the ibrutinib group (95% CI not evaluable) vs 13·3 months (11·3-13·9) in the placebo group (hazard ratio [HR] 0·203, 95% CI 0·150-0·276; p0·0001). IRC-assessed progression-free survival at 18 months was 79% (95% CI 73-83) in the ibrutinib group and 24% (18-31) in the placebo group (HR 0·203, 95% CI 0·150-0·276; p0·0001). The most frequent all-grade adverse events were neutropenia and nausea. 222 (77%) of 287 patients in the ibrutinib group and 212 (74%) of 287 patients in the placebo group reported grade 3-4 events; the most common grade 3-4 adverse events in both groups were neutropenia (154 [54%] in the ibrutinib group vs 145 [51%] in the placebo group) and thrombocytopenia (43 [15%] in each group). A safety profile similar to that previously reported with ibrutinib and bendamustine plus rituximab individually was noted.In patients eligible for bendamustine plus rituximab, the addition of ibrutinib to this regimen results in significant improvements in outcome with no new safety signals identified from the combination and a manageable safety profile.Janssen ResearchDevelopment.

Published
2016

38. Replacing carmustine by thiotepa and cyclophosphamide for autologous stem cell transplantation in Hodgkin’s and non-Hodgkin’s B-cell lymphoma

Author

Joffe, E, primary, Rosenberg, D, additional, Rozovski, U, additional, Perry, C, additional, Kirgner, I, additional, Trestman, S, additional, Gur, O, additional, Aviv, F, additional, Sarid, N, additional, Kolomansky, A, additional, Gepstein, L, additional, Herishanu, Y, additional, and Naparstek, E, additional

Published
2017
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39. Outcome predictors in elderly Hodgkin's lymphoma patients placeholder

Author

Avivi, I., primary, Paran, E., additional, Bentur, O., additional, Neuman, Z., additional, Lavie, D., additional, Nachmias, B., additional, Dally, N., additional, Gutwein, O., additional, Herishanu, Y., additional, Peled, S., additional, Sarid, N., additional, Eldad, D., additional, and Perry, C., additional

Published
2017
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41. CD84 mediates CLL-microenvironment interactions

Author

Marom, A, primary, Barak, A F, additional, Kramer, M P, additional, Lewinsky, H, additional, Binsky-Ehrenreich, I, additional, Cohen, S, additional, Tsitsou-Kampeli, A, additional, Kalchenko, V, additional, Kuznetsov, Y, additional, Mirkin, V, additional, Dezorella, N, additional, Shapiro, M, additional, Schwartzberg, P L, additional, Cohen, Y, additional, Shvidel, L, additional, Haran, M, additional, Becker-Herman, S, additional, Herishanu, Y, additional, and Shachar, I, additional

Published
2016
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47. P-287 Infectious events are much more prevalent following a seven compared to five days cycle of azacitidine regardless of patient's age

Author

Ofran, Y., primary, Filanovsky, K., additional, Gafter-Gvili, A., additional, Vidal, L., additional, Aviv, A., additional, Gatt, M.E., additional, Silbershatz, I., additional, Herishanu, Y., additional, Arad, A., additional, Tadmor, T., additional, Dally, N., additional, Nemets, A., additional, Rouvio, O., additional, Ronson, A., additional, Herzog-Tzarfati, K., additional, Akria, L., additional, Braester, A., additional, Hellmann, I., additional, Yeganeh, S., additional, Nagler, A., additional, Leiba, R., additional, Mittelman, M., additional, and Merkel, D., additional

Published
2013
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48. CD84 is a survival receptor for CLL cells

Author

Binsky-Ehrenreich, I, primary, Marom, A, additional, Sobotta, M C, additional, Shvidel, L, additional, Berrebi, A, additional, Hazan-Halevy, I, additional, Kay, S, additional, Aloshin, A, additional, Sagi, I, additional, Goldenberg, D M, additional, Leng, L, additional, Bucala, R, additional, Herishanu, Y, additional, Haran, M, additional, and Shachar, I, additional

Published
2013
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