Cancer Medicine (2020-11-01)

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

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

DOI
https://doi.org/10.1002/cam4.3470
Journal volume & issue
Vol. 9, no. 22
pp. 8468 – 8479

Abstract

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Abstract 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) 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.

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