Clinical Efficacy of Isatuximab Plus Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients

Eur J Haematol. 2025 Jan;114(1):105-114. doi: 10.1111/ejh.14314. Epub 2024 Oct 6.

Abstract

Isatuximab, a novel anti-CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa-Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real-world efficacy and safety are poorly reported. In this Italian multicenter real-life observational retrospective study, efficacy and safety of the Isa-Kd regimen were evaluated in a cohort of 103 RRMM patients. Overall response rate (ORR) was 85%, with stringent (sCR) or complete response (CR) in 18% of cases and very good partial response (VGPR) in 39%. Median PFS and OS were not reached within the study period, while 1-year PFS and OS were 72% and 77%, respectively. Hematological toxicities were observed in 42% of subjects, and cardiac toxicities occurred in 24% of cases. Moreover, we conducted a subanalysis on patients (N = 69) treated with Isa-Kd after one prior line of therapy, showing an ORR of 88%, with sCR + CR in 20% of subjects, VGPR in 46%, and PR in 22% of patients. In this group, median PFS and OS were not reached, while 1-year PFS and OS were 92% and 95%, respectively. In conclusions, our study confirmed Isa-Kd as an effective treatment option for RRMM with a manageable safety profile even in real-life settings.

Keywords: isatuximab; multiple myeloma; proteasome inhibitors; real life.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Dexamethasone* / administration & dosage
  • Dexamethasone* / adverse effects
  • Dexamethasone* / therapeutic use
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma* / diagnosis
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / mortality
  • Oligopeptides* / administration & dosage
  • Oligopeptides* / adverse effects
  • Oligopeptides* / therapeutic use
  • Recurrence
  • Retrospective Studies
  • Treatment Outcome

Substances

  • carfilzomib
  • Dexamethasone
  • Oligopeptides
  • isatuximab
  • Antibodies, Monoclonal, Humanized