Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance)

J Clin Oncol. 2015 Nov 1;33(31):3635-40. doi: 10.1200/JCO.2014.59.9258. Epub 2015 Aug 24.

Abstract

Purpose: Lenalidomide and rituximab (LR) are active agents in follicular lymphoma (FL). Combination regimens have not been previously assessed in randomized studies.

Patients and methods: The Cancer and Leukemia Group B (Alliance) 50401 trial is a randomized phase II trial studying rituximab (375 mg/m(2) weekly for 4 weeks), lenalidomide (15 mg per day on days 1 to 21, followed by 7 days of rest, in cycle 1 and then 20 mg per day on days 1 to 21, followed by 7 days of rest, in cycles 2 to 12), or LR. The rituximab-alone arm was discontinued as a result of poor accrual. Eligibility included recurrent FL and prior rituximab with time to progression of ≥ 6 months from last dose. Aspirin or heparin was recommended for patients at high thrombosis risk.

Results: Ninety-one patients (lenalidomide, n = 45; LR, n = 46) received treatment; median age was 63 years (range, 34 to 89 years), and 58% were intermediate or high risk according to the Follicular Lymphoma International Prognostic Index. In the lenalidomide and LR arms, grade 3 to 4 adverse events occurred in 58% and 53% of patients, with 9% and 11% of patients experiencing grade 4 toxicity, respectively; grade 3 to 4 adverse events included neutropenia (16% v 20%, respectively), fatigue (9% v 13%, respectively), and thrombosis (16% [n = 7] v 4% [n = 2], respectively; P = .157). Thirty-six percent of lenalidomide patients and 63% of LR patients completed 12 cycles. Lenalidomide alone was associated with more treatment failures, with 22% of patients discontinuing treatment as a result of adverse events. Dose-intensity exceeded 80% in both arms. Overall response rate was 53% (20% complete response) and 76% (39% complete response) for lenalidomide alone and LR, respectively (P = .029). At the median follow-up of 2.5 years, median time to progression was 1.1 year for lenalidomide alone and 2 years for LR (P = .0023).

Conclusion: LR is more active than lenalidomide alone in recurrent FL with similar toxicity, warranting further study in B-cell non-Hodgkin lymphoma as a platform for addition of novel agents.

Trial registration: ClinicalTrials.gov NCT00238238.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Aspirin / therapeutic use
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Heparin / therapeutic use
  • Humans
  • Kaplan-Meier Estimate
  • Lenalidomide
  • Lymphoma, Follicular / drug therapy*
  • Lymphoma, Follicular / mortality
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Risk Factors
  • Rituximab / administration & dosage*
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives*
  • Thrombosis / complications
  • Thrombosis / drug therapy
  • Treatment Outcome

Substances

  • Rituximab
  • Thalidomide
  • Heparin
  • Lenalidomide
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT00238238