Matching-Adjusted Indirect Treatment Comparison to Assess the Comparative Efficacy of Ciltacabtagene Autoleucel in CARTITUDE-1 Versus Belantamab Mafodotin in DREAMM-2, Selinexor-Dexamethasone in STORM Part 2, and Melphalan Flufenamide-Dexamethasone in HORIZON for the Treatment of Patients With Triple-Class Exposed Relapsed or Refractory Multiple Myeloma

Clin Lymphoma Myeloma Leuk. 2022 Sep;22(9):690-701. doi: 10.1016/j.clml.2022.04.025. Epub 2022 May 23.

Abstract

Introduction: This study estimated the comparative efficacy of ciltacabtagene autoleucel (cilta-cel; CARTITUDE-1), a chimeric antigen receptor (CAR)-T-cell therapy, versus 3 non-CAR-T therapies (belantamab mafodotin [DREAMM-2], selinexor plus dexamethasone [STORM Part 2], and melphalan flufenamide plus dexamethasone [HORIZON]), each with distinct mechanisms of action, for the treatment of patients with relapsed or refractory multiple myeloma (RRMM) who were triple-class exposed to an immunomodulatory drug, proteasome inhibitor, and an anti-CD38 monoclonal antibody.

Patients and methods: Pairwise matching-adjusted indirect treatment comparisons (MAICs) were conducted using patient-level data for cilta-cel from CARTITUDE-1 and summary level data for each comparator (2.5 mg/kg cohort in DREAMM-2, modified intention-to-treat population in STORM Part 2, and triple-class refractory patients in HORIZON). Treated patients from CARTITUDE-1 who satisfied the eligibility of the comparator trial were included. MAICs adjusted for imbalances in important prognostic factors between CARTITUDE-1 and the comparator populations. Comparative efficacy of cilta-cel versus each therapy was estimated for overall response rate, complete response or better rate, progression-free survival, and overall survival.

Results: After adjustment, patients treated with cilta-cel demonstrated at least a 3.1-fold and at least a 10.3-fold increase in the likelihood of achieving an overall response or complete response or better, respectively, at least a 74% reduction in the risk of disease progression or death, and at least a 47% reduction in the risk of death. These results were statistically significant.

Conclusion: Cilta-cel showed improved efficacy over each comparator for all outcomes, demonstrating its potential as an efficacious treatment for patients with triple-class exposed RRMM.

Keywords: Cilta-cel; Indirect comparison; RRMM.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use
  • Humans
  • Hydrazines
  • Melphalan / pharmacology
  • Melphalan / therapeutic use
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / etiology
  • Triazoles

Substances

  • Antibodies, Monoclonal, Humanized
  • Hydrazines
  • Triazoles
  • selinexor
  • Dexamethasone
  • belantamab mafodotin
  • Melphalan