Pomalidomide/Daratumumab/Dexamethasone in Relapsed or Refractory Multiple Myeloma: Final Overall Survival From MM-014

Clin Lymphoma Myeloma Leuk. 2024 Dec;24(12):852-862. doi: 10.1016/j.clml.2024.07.014. Epub 2024 Aug 8.

Abstract

Background: Patients with relapsed or refractory multiple myeloma (RRMM) who have exhausted lenalidomide benefits require improved therapies. The 3-cohort phase 2 MM-014 trial (NCT01946477) explored pomalidomide in early lines of treatment for lenalidomide-exposed RRMM. In cohort B, pomalidomide plus daratumumab and dexamethasone (DPd) showed promising efficacy (median follow-up 28.4 months), as previously reported. Here, we report final overall survival (OS) in cohort B.

Methods: Patients aged ≥ 18 years were treated in 28-day cycles: pomalidomide 4 mg orally daily from days 1 to 21; daratumumab 16 mg/kg intravenously on days 1, 8, 15, and 22 (cycles 1-2), days 1 and 15 (cycles 3-6), and day 1 (cycle ≥ 7); and dexamethasone 40 mg (age ≤ 75 years) or 20 mg (age > 75 years) orally on days 1, 8, 15, and 22. The primary endpoint was ORR. OS and safety were secondary endpoints.

Results: Among 112 patients enrolled, 85 (75.9%) had lenalidomide-refractory disease and 27 (24.1%) had lenalidomide-relapsed disease. At a median follow-up of 41.9 months (range, 0.4-73.1), median OS was 56.7 months (95% confidence interval, 46.5-not reached). Treatment-emergent adverse events related to, and leading to discontinuation of, pomalidomide, dexamethasone, or daratumumab occurred in 7 (6.3%), 9 (8.0%), and 6 (5.4%) patients, respectively.

Conclusion: With long-term follow-up, our results show favorable OS with DPd. The safety profile was consistent with previous reports, with no new safety signals identified. IMiD agent-based therapy can still be considered in patients with RRMM who experience progressive disease on or after lenalidomide.

Keywords: DPd; Efficacy; Immunomodulatory agent; Lenalidomide-exposed; Toxicity management.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal* / administration & dosage
  • Antibodies, Monoclonal* / pharmacology
  • Antibodies, Monoclonal* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Dexamethasone* / administration & dosage
  • Dexamethasone* / therapeutic use
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / mortality
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / mortality
  • Thalidomide* / administration & dosage
  • Thalidomide* / analogs & derivatives
  • Thalidomide* / pharmacology
  • Thalidomide* / therapeutic use
  • Treatment Outcome

Substances

  • pomalidomide
  • Thalidomide
  • Dexamethasone
  • daratumumab
  • Antibodies, Monoclonal