Journal Article

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

de la Serna, Javier, Ujjani, Chaitra S., Piciocchi, Alfonso, Cimino, Giuseppe, Di Raimondo, Francesco, Cavallari, Maurizio, Shadman, Mazyar, Gaidano, Gianluca, Shah, Nirav N., Doubek, Michael, Cucci, Rosalba, Laurenti, Luca, Tam, Constantine S., Billio, Atto, Pagel, John M., Ferrarini, Isacco, Mato, Anthony R., Trentin, Livio, Allan, John N., Brander, Danielle M., Gentile, Massimo, Winter, Allison, Pu, Jeffrey J., Molica, Stefano, Rigolin, Gian Matteo, Lamanna, Nicole, Barr, Paul M., Mauro, Francesca Romana, Spacek, Martin, Vignetti, Marco, Hill, Brian T., Medina Perez, Angeles, Cuneo, Antonio, Lansigan, Frederick, Orlandi, Ester Maria, Jacobs, Ryan, Roeker, Lindsey, Marchetti, Monia, Foà, Robin, Coscia, Marta, Sehgal, Alison R., Schuster, Stephen J., Ilariucci, Fiorella, Tedeschi, Alessandra, Skarbnik, Alan P., Ghia, Paolo, Farina, Lucia

2020

Overview

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. Bendamustine and Rituximab was a relatively effective first‐line regimen in real‐world untreated CLL patients with reduced renal function or coexisting conditions without TP53 disruption.In a matched‐adjusted indirect comparison with a cohort of CLL patients treated upfront, ibrutinib provided longer PFS than bendamustine and rituximab in those with advanced stage.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Age / bendamustine / Chronic lymphocytic leukemia / Clinical Cancer Research / Clinical medicine / Clinical trials / Creatinine / Disease control / ibrutinib / Immunotherapy / Inhibitor drugs / Leukemia / Lymphatic leukemia / Monoclonal antibodies / Mutation / Original Research / p53 Protein / real‐world analysis / Renal function / Rituximab / Survival / Targeted cancer therapy / unfit patients