Lenalidomide treatment and prognostic markers in relapsed or refractory chronic lymphocytic leukemia: data from the prospective, multicenter phase-II CLL-009 trial

Blood Cancer J. 2016 Mar 11;6(3):e404. doi: 10.1038/bcj.2016.9.

Abstract

Efficacy of lenalidomide was investigated in 103 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) treated on the prospective, multicenter randomized phase-II CLL-009 trial. Interphase cytogenetic and mutational analyses identified TP53 mutations, unmutated IGHV, or del(17p) in 36/96 (37.5%), 68/88 (77.3%) or 22/92 (23.9%) patients. The overall response rate (ORR) was 40.4% (42/104). ORRs were similar irrespective of TP53 mutation (36.1% (13/36) vs 43.3% (26/60) for patients with vs without mutation) or IGHV mutation status (45.0% (9/20) vs 39.1% (27/68)); however, patients with del(17p) had lower ORRs than those without del(17p) (21.7% (5/22) vs 47.1% (33/70); P=0.049). No significant differences in progression-free survival and overall survival (OS) were observed when comparing subgroups defined by the presence or absence of high-risk genetic characteristics. In multivariate analyses, only multiple prior therapies (⩾3 lines) significantly impacted outcomes (median OS: 21.2 months vs not reached; P=0.019). This analysis indicates that lenalidomide is active in patients with relapsed/refractory CLL with unfavorable genetic profiles, including TP53 inactivation or unmutated IGHV. (ClinicalTrials.gov identifier: NCT00963105).

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Drug Resistance, Neoplasm*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunologic Factors / therapeutic use*
  • Lenalidomide
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis*
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • Recurrence
  • Retreatment
  • Survival Analysis
  • Thalidomide / analogs & derivatives*
  • Thalidomide / therapeutic use
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Antineoplastic Agents
  • Immunoglobulin Heavy Chains
  • Immunologic Factors
  • Tumor Suppressor Protein p53
  • Thalidomide
  • Lenalidomide

Associated data

  • ClinicalTrials.gov/NCT00963105