Tumor flare reaction associated with lenalidomide treatment in patients with chronic lymphocytic leukemia predicts clinical response

Cancer. 2011 May 15;117(10):2127-35. doi: 10.1002/cncr.25748. Epub 2010 Nov 29.

Abstract

Background: In patients with chronic lymphocytic leukemia (CLL), treatment with lenalidomide induces a unique, previously uncharacterized, immune response called tumor flare reaction (TFR). The clinical significance of this reaction remains unknown.

Methods: Forty-five patients with CLL who were treated with lenalidomide in a phase 2 clinical trial were evaluated for the clinical features, intensity, and duration of TFR. Correlation was made with tumor response and the immune cellular microenvironment. Steroids for the prophylaxis of TFR was not given to patients in Group A (n = 29) whereas patients in Group B (n = 16) received low-dose prednisone as well as a slow dose escalation of lenalidomide for the prevention of TFR.

Results: Thirty (67%) patients experienced a TFR, with a grade 2 or 3 reaction (according to National Cancer Institute Common Toxicity Criteria [version 3.0]) observed in 33% of patients (47% in Group A and 9% in Group B; P = .05). The median time to onset of the TFR was 6 days, and was longer in the patients receiving prophylaxis (4 days vs 9 days, respectively; P = .01). A complete response was observed in 7 of 30 (23%) patients with TFR and 1 of 15 (7%) patients without TFR. The median progression-free survival was 19.9 months and 19.4 months, respectively, for patients with versus those without TFR (P = .92).

Conclusions: TFR is a unique immune-mediated phenomenon noted with lenalidomide treatment only in patients with CLL that correlates with clinical response. It can be effectively managed with anti-inflammatory agents.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Female
  • Humans
  • Immunity, Cellular / drug effects
  • Lenalidomide
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Male
  • Middle Aged
  • Risk Factors
  • Thalidomide / adverse effects
  • Thalidomide / analogs & derivatives*
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Thalidomide
  • Lenalidomide