Extended Treatment with Single-Agent Ibrutinib at the 420 mg Dose Leads to Durable Responses in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Academic Article uri icon

Overview

abstract

  • Purpose: Ibrutinib, a first-in-class, once-daily, oral inhibitor of Bruton tyrosine kinase, promotes apoptosis, and inhibits B-cell proliferation, adhesion, and migration. Ibrutinib has demonstrated single-agent efficacy and acceptable tolerability at doses of 420 and 840 mg in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who were treatment-naïve (TN) or had relapsed/refractory (R/R) CLL after ≥1 prior therapy in a phase Ib/II study (PCYC-1102). Subsequently, the ibrutinib 420 mg dose was approved in CLL.Experimental Design: We report data with 44 months of follow-up on 94 patients with TN and R/R CLL/SLL receiving ibrutinib 420 mg once-daily in PCYC-1102 and the long-term extension study PCYC-1103.Results: Ninety-four CLL/SLL patients (27 TN, 67 R/R) were treated with ibrutinib (420 mg/day). Patients with R/R disease had received a median of four prior therapies (range, 1-12). Responses were rapid and durable and median duration of response was not reached. Best overall response was 91% [85% TN (complete response, CR 26%) and 94% R/R (9% CR)]. Median progression-free survival (PFS) was not reached in either group. The 30-month PFS rate was 96% and 76% for TN and R/R patients, respectively. Ibrutinib was well tolerated with extended follow-up; rates of grade ≥3 cytopenias and fatigue, as well as discontinuations due to toxicities decreased over time.Conclusions: Single-agent ibrutinib at 420 mg once-daily resulted in durable responses and was well tolerated with up to 44 months follow-up in patients with TN and R/R CLL/SLL. Currently, 66% of patients continue on ibrutinib. Clin Cancer Res; 23(5); 1149-55. ©2017 AACR.

authors

  • Coutré, Steven E
  • Furman, Richard R
  • Flinn, Ian W
  • Burger, Jan A
  • Blum, Kristie
  • Sharman, Jeff
  • Jones, Jeffrey
  • Wierda, William
  • Zhao, Weiqiang
  • Heerema, Nyla A
  • Johnson, Amy J
  • Tran, Anh
  • Zhou, Cathy
  • Bilotti, Elizabeth
  • James, Danelle F
  • Byrd, John C
  • O'Brien, Susan

publication date

  • January 10, 2017

Research

keywords

  • Drug-Related Side Effects and Adverse Reactions
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines

Identity

PubMed Central ID

  • PMC6317338

Scopus Document Identifier

  • 85014732783

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-16-1431

PubMed ID

  • 28073846

Additional Document Info

volume

  • 23

issue

  • 5