Cilta-cel, a BCMA-targeting CAR-T therapy for patients with multiple myeloma

Expert Opin Biol Ther. 2024 May;24(5):339-350. doi: 10.1080/14712598.2024.2352591. Epub 2024 May 13.

Abstract

Introduction: Ciltacabtagene autoleucel (cilta-cel), a BCMA-targeting CAR-T therapy, is approved in the United States and Europe for patients with relapsed/refractory multiple myeloma (RRMM) and ≥1 prior line of therapy (LOT), including a proteasome inhibitor and an immunomodulatory drug, and are lenalidomide refractory.

Areas covered: We examine recent long-term data in heavily pretreated RRMM (LEGEND-2, CARTITUDE-1) and earlier LOTs (CARTITUDE-4) compared with standard therapy and discuss the rationale for investigating cilta-cel as frontline therapy for transplant-eligible and transplant-ineligible patients (CARTITUDE-5, CARTITUDE-6).

Expert opinion: CAR-T therapies can improve outcomes for patients with MM across different LOTs. CARTITUDE-1 and CARTITUDE-4 have set a new bar for efficacy, with median PFS of 34.9 months in heavily pretreated patients (CARTITUDE-1) and a 74% relative risk reduction for progression/death versus standard care in patients with 1-3 prior LOTs (CARTITUDE-4), with manageable safety. Response rates were consistent between the two studies: 98% in CARTITUDE-1 and approaching 100% for infused patients in CARTITUDE-4. Cilta-cel could be a key treatment choice for patients with RRMM after first LOT. Clinical trials investigating frontline cilta-cel therapy will provide valuable insights into optimizing treatment pathways with the aim to potentially cure MM.

Keywords: B-cell maturation antigen (BCMA); chimeric antigen receptor (CAR)-T–cell therapy; ciltacabtagene autoleucel (cilta-cel); lenalidomide-refractory; multiple myeloma; newly diagnosed multiple myeloma; progression-free survival; relapsed/refractory multiple myeloma.

Publication types

  • Review

MeSH terms

  • B-Cell Maturation Antigen* / immunology
  • Biological Products / adverse effects
  • Biological Products / therapeutic use
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Multiple Myeloma* / immunology
  • Multiple Myeloma* / mortality
  • Multiple Myeloma* / therapy
  • Receptors, Chimeric Antigen / immunology

Substances

  • B-Cell Maturation Antigen
  • TNFRSF17 protein, human
  • axicabtagene ciloleucel
  • Biological Products
  • Receptors, Chimeric Antigen