Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study

Jan A. Burger, Paul M. Barr, Tadeusz Robak, Carolyn Owen, Paolo Ghia, Alessandra Tedeschi, Osnat Bairey, Peter Hillmen, Steven E. Coutre, Stephen Devereux, Sebastian Grosicki, Helen McCarthy, David Simpson, Fritz Offner, Carol Moreno, Sandra Dai, Indu Lal, James P. Dean, Thomas J. Kipps

Research output: Contribution to journalArticlepeer-review

Abstract

RESONATE-2 is a phase 3 study of first-line ibrutinib versus chlorambucil in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Patients aged ≥65 years (n = 269) were randomized 1:1 to once-daily ibrutinib 420 mg continuously or chlorambucil 0.5–0.8 mg/kg for ≤12 cycles. With a median (range) follow-up of 60 months (0.1–66), progression-free survival (PFS) and overall survival (OS) benefits for ibrutinib versus chlorambucil were sustained (PFS estimates at 5 years: 70% vs 12%; HR [95% CI]: 0.146 [0.098–0.218]; OS estimates at 5 years: 83% vs 68%; HR [95% CI]: 0.450 [0.266–0.761]). Ibrutinib benefit was also consistent in patients with high prognostic risk (TP53 mutation, 11q deletion, and/or unmutated IGHV) (PFS: HR [95% CI]: 0.083 [0.047–0.145]; OS: HR [95% CI]: 0.366 [0.181–0.736]). Investigator-assessed overall response rate was 92% with ibrutinib (complete response, 30%; 11% at primary analysis). Common grade ≥3 adverse events (AEs) included neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), and hyponatremia (6%); occurrence of most events as well as discontinuations due to AEs decreased over time. Fifty-eight percent of patients continue to receive ibrutinib. Single-agent ibrutinib demonstrated sustained PFS and OS benefit versus chlorambucil and increased depth of response over time.

Original languageEnglish
Pages (from-to)787-798
Number of pages12
JournalLeukemia
Volume34
Issue number3
DOIs
Publication statusPublished - Mar 1 2020

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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