Lower-risk MDS: lenalidomide dose reductions show benefit in phase 3 trial

  • Garcia-Manero G & al.
  • Clin Lymphoma Myeloma Leuk
  • 21 Dec 2018

  • curated by David Reilly
  • Univadis Clinical Summaries
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Takeaway

  • In patients with lower-risk, non-del(5q) myelodysplastic syndromes (MDS) who were ineligible for/refractory to erythropoiesis-stimulating agents (ESAs), lenalidomide demonstrated a higher rate of clinical benefit vs placebo despite an increased incidence of hematologic adverse events (AEs).
  • Lenalidomide dose reductions may have enabled patients to continue receiving treatment longer.

Why this matters

  • Paradoxically, reduced lenalidomide dose can improve outcomes in some patients.

Study design

  • Analysis of the phase 3 MDS-005 study to compare benefit-risk profiles of lenalidomide (n=160) and placebo (n=79) in 239 red blood cell transfusion-dependent (RBC-TD) patients with lower-risk, non-del(5q) MDS ineligible for ESAs.
  • Funding: Celgene Corporation.

Key results

  • 31.9% achieved clinical benefit with lenalidomide vs 3.8% with placebo: OR, 11.85 (95% CI, 3.57-39.38); relative risk (RR), 8.39 (95% CI, 2.70-26.06).
  • 31.9% of patients discontinued lenalidomide because of a treatment-emergent AE (TEAE).
  • Compared with patients without lenalidomide dose reductions, patients with ≥1 dose reduction were more likely to achieve:
    • Clinical benefit ≥8 weeks: 47% vs 18%; OR, 3.98 (95% CI, 1.94-8.15).
    • RBC-TI ≥8 weeks: 39% vs 16%; OR, 3.44 (95% CI, 1.63-7.26).
    • Longer median duration of response: 29.6 (range, 8.1-123.7) weeks vs 23.7 (range, 9.9-103.7) weeks.

Limitations

  • Retrospective data.