Efficacy of bendamustine and rituximab in unfit patients with previously untreated chronic lymphocytic leukemia. Indirect comparison with ibrutinib in a real-world setting. A GIMEMA-ERIC and US study.

Autor: Cuneo A; Hematology, Department of Medical Sciences, St. Anna University Hospital, Ferrara, Italy., Mato AR; Division of Hematological Oncology, CLL Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Rigolin GM; Hematology, Department of Medical Sciences, St. Anna University Hospital, Ferrara, Italy., Piciocchi A; Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy., Gentile M; Department of Onco-Hematology, Hematology Unit, A.O. of Cosenza, Cosenza, Italy., Laurenti L; Department of Radiological, Radiotherapeutic and Hematological Sciences, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Rome, Italy., Allan JN; Weill Cornell Medicine, New York, NY, USA., Pagel JM; Center for Blood Disorders and Stem Cell Transplantation, Swedish Cancer Institute, Seattle, WA, USA., Brander DM; Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC, USA., Hill BT; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA., Winter A; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA., Lamanna N; Columbia University Medical Center, New York, NY, USA., Tam CS; Peter McCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia., Jacobs R; Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Carolinas Healthcare System, Charlotte, NC, USA., Lansigan F; Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA., Barr PM; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA., Shadman M; Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, Seattle, WA, USA., Skarbnik AP; Lymphoproliferative Disorders Program, Novant Health Cancer Institute, Charlotte, NC, USA., Pu JJ; SUNY Upstate Medical University, SUNY Upstate Medical University, Syracuse, NY, USA., Sehgal AR; University of Pittsburgh, Pittsburgh, PA, USA., Schuster SJ; Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA., Shah NN; Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, USA., Ujjani CS; Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, Seattle, WA, USA., Roeker L; Division of Hematological Oncology, CLL Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Orlandi EM; Hematology Unit, IRCCS Policlinico San Matteo, Pavia, Italy., Billio A; Hematology and Transplant Unit, San Maurizio Hospital, Azienda Sanitaria dell'Alto Adige, Bolzano, Italy., Trentin L; Hematology and Clinical Immunology, Department of Medicine, University of Padua, Padua, Italy., Spacek M; Department of Medicine, Department of Hematology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic., Marchetti M; Oncology Unit, Cardinal Massaia Hospital, Asti, Italy., Tedeschi A; Hematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy., Ilariucci F; Hematology, Azienda USL-IRCCS, Reggio Emilia, Italy., Gaidano G; Division of Hematology, Department of Translational Medicine, University of eastern Piedmont, Novara, Italy., Doubek M; Department of Internal Medicine - Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic., Farina L; Hematology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy., Molica S; Hematology Unit, A. Pugliese Hospital, Azienda Ospedaliera Pugliese Ciaccio, Catanzaro, Italy., Di Raimondo F; Catania Università di Catania, Cattedra di Ematologia, Catania, Italy., Coscia M; Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino and Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy., Mauro FR; Hematology, Department of Translational and Precision Medicine, 'Sapienza' University, Rome, Italy., de la Serna J; Hematology Unit, Hospital Universitario, Madrid, Spain., Medina Perez A; Hospital Costa del Sol, Marbella, Spain., Ferrarini I; Hematology, Department of Cell Therapy and Hematology, University Hospital, Verona, Italy., Cimino G; Department of Translational and Precision Medicine, University 'La Sapienza', UOC di Ematologia con Trapianto, Ospedale S. Maria Goretti, Latina, Italy., Cavallari M; Hematology, Department of Medical Sciences, St. Anna University Hospital, Ferrara, Italy., Cucci R; Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy., Vignetti M; Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy., Foà R; Hematology, Department of Translational and Precision Medicine, 'Sapienza' University, Rome, Italy., Ghia P; Strategic Research Program on CLL, Division of Experimental Oncology, IRCCS Ospedale San Raffaele, Università Vita-Salute San Raffaele, Milan, Italy.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2020 Nov; Vol. 9 (22), pp. 8468-8479. Date of Electronic Publication: 2020 Sep 24.
DOI: 10.1002/cam4.3470
Abstrakt: Limited information is available on the efficacy of front-line bendamustine and rituximab (BR) in chronic lymphocytic leukemia (CLL) with reduced renal function or coexisting conditions. We therefore analyzed a cohort of real-world patients and performed a matched adjusted indirect comparison with a cohort of patients treated with ibrutinib. One hundred and fifty-seven patients with creatinine clearance (CrCl) <70 mL/min and/or CIRS score >6 were treated with BR. The median age was 72 years; 69% of patients had ≥2 comorbidities and the median CrCl was 59.8 mL/min. 17.6% of patients carried TP53 disruption. The median progression-free survival (PFS) was 45 months; TP53 disruption was associated with a shorter PFS (P = 0.05). The overall survival (OS) at 12, 24, and 36 months was 96.2%, 90.1%, and 79.5%, respectively. TP53 disruption was associated with an increased risk of death (P = 0.01). Data on 162 patients ≥65 years treated with ibrutinib were analyzed and compared with 165 patients ≥65 years treated with BR. Factors predicting for a longer PFS at multivariable analysis in the total patient population treated with BR and ibrutinib were age (HR 1.06, 95% CI 1.02-1.10, P < 0.01) and treatment with ibrutinib (HR 0.55, 95% CI 0.33-0.93, P = 0.03). In a post hoc analysis of patients in advanced stage, a significant PFS advantage was observed in patient who had received ibrutinib (P = 0.03), who showed a trend for OS advantage (P = 0.08). We arrived at the following conclusions: (a) BR is a relatively effective first-line regimen in a real-world population of unfit patients without TP53 disruption, (b) ibrutinib provided longer disease control than BR in patients with advanced disease stage.
(© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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