Matching-adjusted indirect comparison of isatuximab plus carfilzomib and dexamethasone with daratumumab plus lenalidomide and dexamethasone in relapsed multiple myeloma

Cancer Med. 2023 Apr;12(7):8005-8017. doi: 10.1002/cam4.5584. Epub 2023 Feb 1.

Abstract

Backgound: Lenalidomide-based regimens are commonly used for early relapse in patients with relapsed and/or refractory multiple myeloma (RRMM) receiving at least one prior line of therapy. In the absence of head-to-head comparison, matching-adjusted indirect comparison (MAIC) was conducted to demonstrate efficacy and safety of isatuximab+carfilzomib+dexamethasone (Isa-Kd) versus daratumumab + lenalidomide + dexamethasone (Dara-Rd) in RRMM.

Methods: Patient-level data from IKEMA trial (Isa-Kd, n = 179) were matched to aggregate data from POLLUX (Dara-Rd, n = 286). Hazard ratios (HR) and 95% confidence intervals (CI) for progression-free survival (PFS) and overall survival (OS) were generated by weighted Cox proportional hazard models. Odds ratios (OR), 95% CI, and p-value were calculated for ≥very good partial response (≥VGPR) and treatment-emergent adverse events (TEAEs).

Results: After matching, no significant differences were observed between Isa-Kd and Dara-Rd in baseline characteristics except for patients with >3 prior lines (0.0% vs. 4.9%). Isa-Kd showed significantly better PFS (HR [95% CI]: 0.46 [0.24-0.86]; p = 0.0155), statistically non-significant improvement favoring Isa-Kd in OS (0.47 [0.20-1.09]; 0.0798), and ≥VGPR (OR [95% CI]: 1.53 [0.89-2.64]; p = 0.1252) than Dara-Rd. Odds of occurrence were significantly lower for some all-grade and grade 3/4 TEAEs with Isa-Kd than Dara-Rd.

Conclusion: These results support Isa-Kd as an efficacious treatment for early relapse in non-lenalidomide refractory patients.

Keywords: comparative efficacy; daratumumab; isatuximab; matching-adjusted indirect comparison; relapsed refractory multiple myeloma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Dexamethasone / adverse effects
  • Humans
  • Lenalidomide / adverse effects
  • Multiple Myeloma*
  • Neoplasm Recurrence, Local / drug therapy
  • Recurrence

Substances

  • Lenalidomide
  • daratumumab
  • isatuximab
  • carfilzomib
  • Dexamethasone