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.
bendamustine; chronic lymphocytic leukemia; ibrutinib; real-world analysis; unfit patients
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)/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.
Cuneo, Antonio; Mato, Anthony R; Rigolin, Gian Matteo; Piciocchi, Alfonso; Gentile, Massimo; Laurenti, Luca; Allan, John N; Pagel, John M; Brander, Danielle M; Hill, Brian T; Winter, Allison; Lamanna, Nicole; Tam, Constantine S; Jacobs, Ryan; Lansigan, Frederick; Barr, Paul M; Shadman, Mazyar; Skarbnik, Alan P; Pu, Jeffrey J; Sehgal, Alison R; Schuster, Stephen J; Shah, Nirav N; Ujjani, Chaitra S; Roeker, Lindsey; Orlandi, Ester Maria; Billio, Atto; Trentin, Livio; Spacek, Martin; Marchetti, Monia; Tedeschi, Alessandra; Ilariucci, Fiorella; Gaidano, Gianluca; Doubek, Michael; Farina, Lucia; Molica, Stefano; Di Raimondo, Francesco; Coscia, Marta; Mauro, Francesca Romana; de la Serna, Javier; Medina Perez, Angeles; Ferrarini, Isacco; Cimino, Giuseppe; Cavallari, Maurizio; Cucci, Rosalba; Vignetti, Marco; Foà, Robin; Ghia, Paolo; and GIMEMA, European Research Initiative (ERIC) on CLL, US study group, "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." (2020). Articles, Abstracts, and Reports. 3724.