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.

Catania Università di Catania Cattedra di Ematologia Catania Italy

Center for Blood Disorders and Stem Cell Transplantation Swedish Cancer Institute Seattle WA USA

Columbia University Medical Center New York NY USA

Dartmouth Hitchcock Medical Center Lebanon NH USA

Department of Hematologic Oncology and Blood Disorders Levine Cancer Institute Carolinas Healthcare System Charlotte NC USA

Department of Internal Medicine Hematology and Oncology University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Department of Medicine Department of Hematology 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Onco Hematology Hematology Unit A O of Cosenza Cosenza Italy

Department of Radiological Radiotherapeutic and Hematological Sciences Fondazione Policlinico Universitario A Gemelli IRCCS Rome Italy

Department of Translational and Precision Medicine University La Sapienza UOC di Ematologia con Trapianto Ospedale S Maria Goretti Latina Italy

Division of Hematologic Malignancies and Cellular Therapy Duke University Durham NC USA

Division of Hematological Oncology CLL Program Memorial Sloan Kettering Cancer Center New York NY USA

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

Division of Hematology and Oncology Medical College of Wisconsin Milwaukee WI USA

Division of Hematology and Oncology University of Pennsylvania Philadelphia PA USA

Division of Hematology Department of Translational Medicine University of eastern Piedmont Novara Italy

Fred Hutchinson Cancer Research Center Seattle Cancer Care Alliance Seattle WA USA

Hematology and Clinical Immunology Department of Medicine University of Padua Padua Italy

Hematology and Transplant Unit San Maurizio Hospital Azienda Sanitaria dell'Alto Adige Bolzano Italy

Hematology Azienda USL IRCCS Reggio Emilia Italy

Hematology Department Fondazione IRCCS Istituto Nazionale Tumori Milano Italy

Hematology Department of Cell Therapy and Hematology University Hospital Verona Italy

Hematology Department of Medical Sciences St Anna University Hospital Ferrara Italy

Hematology Department of Translational and Precision Medicine Sapienza University Rome Italy

Hematology Niguarda Cancer Center ASST Grande Ospedale Metropolitano Niguarda Milan Italy

Hematology Unit A Pugliese Hospital Azienda Ospedaliera Pugliese Ciaccio Catanzaro Italy

Hematology Unit Hospital Universitario Madrid Spain

Hematology Unit IRCCS Policlinico San Matteo Pavia Italy

Hospital Costa del Sol Marbella Spain

Italian Group for Adult Hematologic Diseases Data Center and Health Outcomes Research Unit Rome Italy

Lymphoproliferative Disorders Program Novant Health Cancer Institute Charlotte NC USA

Oncology Unit Cardinal Massaia Hospital Asti Italy

Peter McCallum Cancer Centre University of Melbourne Melbourne Victoria Australia

Strategic Research Program on CLL Division of Experimental Oncology IRCCS Ospedale San Raffaele Università Vita Salute San Raffaele Milan Italy

SUNY Upstate Medical University SUNY Upstate Medical University Syracuse NY USA

Taussig Cancer Institute Cleveland Clinic Cleveland OH USA

University of Pittsburgh Pittsburgh PA USA

Weill Cornell Medicine New York NY USA

Wilmot Cancer Institute University of Rochester Medical Center Rochester NY USA

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