Randomized phase II results – lenalidomide is not a viable option post-allogeneic stem cell transplant for persistent Chronic Lymphocytic Leukemia

This month, in Biology of Blood and Marrow Transplantation, Maria R. Khouri from The University of Texas MD Anderson Cancer Center, Houston, Texas, USA, et al. published results of their randomized, phase II trial (NCT00899431) investigating non-myeloablative Allogeneic Stem Cell Transplantation (allo-SCT) with or without lenalidomide for Chronic Lymphocytic Leukemia (CLL).

The study was conducted at the MD Anderson Cancer Center between May 2009 and November 2012. Patients with persistent CLL who did not demonstrate signs of Graft versus Host Disease (GvHD) 90–100 days beyond allo-SCT were randomly assigned at a ratio of 1:1 to receive either lenalidomide or standard care (withdrawal of immunosuppression followed by donor lymphocyte infusion). The initial dose of lenalidomide was 5mg every other day and was increased to 10mg daily if tolerated.

Key Highlights:
  • Overall, 38 pts enrolled; 21 (55%) did not meet randomization criteria
  • Nine pts randomized to standard care and 8 pts randomized to lenalidomide
  • MTD of lenalidomide was 5mg every other day in 3 pts and 10mg orally daily in 4 pts
  • One of the 8 pts randomized to lenalidomide refused to take the drug
  • Fifty-seven percent (4/7) discontinued lenalidomide due to acute liver toxicity and neuropathy (n=1, 14%) or acute GvHD (n=3, 43%) occurring at days 4, 22, 30, and 37 after drug initiation
  • Median duration of lenalidomide administration = 61 days (range, 0–338)
  • Best responses = 1 CR and 2 PRs; all 3 initial responders experienced subsequent CLL relapse
  • Immunomodulation took place in 57% of lenalidomide pts and 56% of standard care pts
  • Thirty-three percent (3/9) standard care pts remain alive and in CR at 24+, 24, and 48+ months
  • Median follow-up of all 38 enrolled pts = 2.6 years (range, 1.1–5.4) after allo-SCT
  • For whole group: estimated 3-year OS = 51% (95% CI, 0.36–0.73); estimated 3-year PFS = 38% (95% CI, 0.38–0.62)
  • Median OS: lenalidomide pts = 3.4 years; standard care pts = not reached
  • Median PFS: lenalidomide pts = 1.9 years; standard care pts = not reached
  • Cumulative incidence rate of acute grade 2–4 GvHD: lenalidomide pts = 43% (95% CI, 0.12–0.88); standard care pts = 11% (95% CI, 0–0.33)

Upon the MD Anderson Cancer Center’s data and safety board’s recommendations, the trial was closed early due to “slow accrual, poor tolerance of lenalidomide, and lack of benefit in the patients who received it.”

The authors state that this is the first randomized study with the aim of assessing the use of lenalidomide 90–100 days post-allo-SCT in patients with persistent CLL. The group concluded that lenalidomide is not a viable option in this patient subset and other strategies are required to safely and effectively treat and manage persistent CLL.


In patients with chronic lymphocytic leukemia (CLL), persistence of disease after allogeneic stem cell transplantation (alloSCT) can result in poor outcomes. In an effort to improve these outcomes, patients with persistent CLL who were 90 to 100 days beyond alloSCT with no evidence of graft-versus-host-disease (GVHD) were randomized to receive lenalidomide or standard care (withdrawal of immunosuppression followed by donor lymphocyte infusion). Lenalidomide was initiated at 5 mg every other day and increased to 10 mg daily, if tolerated, in each patient. Of 38 patients enrolled, 17 (45%) met the eligibility criteria for randomization. Of these 17 patients, 8 were randomized to undergo lenalidomide therapy. Five (62%) patients had to stop taking the drug because of toxicity. The main reason for drug discontinuation was acute GVHD in 43% of patients. This incidence was 11% in the patients who were randomized to not receive lenalidomide. With a median follow-up of 2.6 years, the median survival was 3.4 years for those receiving lenalidomide. This was not reached in patients randomized to not receive lenalidomide and in patients in complete remission who were not randomized. These results suggested that treatments other than lenalidomide are needed for persistent CLL after alloSCT.

  1. Khouri M.R. et al. Feasibility of Lenalidomide Therapy for Persistent Chronic Lymphocytic Leukemia after Allogeneic Transplantation. Biology of Blood and Marrow Transplantation. 2017 Aug;23(8):1405-1410. DOI: 10.1016/j.bbmt.2017.04.027. Epub 2017 May 8.