Ciltacabtagene Autoleucel Versus Idecabtagene Vicleucel in Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma with 2-4 Prior Lines of Therapy: Updated Matching-Adjusted Indirect Comparison

Adv Ther. 2026 Mar;43(3):1327-1340. doi: 10.1007/s12325-025-03479-y. Epub 2026 Feb 2.

Abstract

Introduction: The relative efficacy of ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) in relapsed/refractory multiple myeloma (RRMM) was assessed via unanchored matching-adjusted indirect comparison (MAIC) using data from the CARTITUDE-4 and CARTITUDE-1 (cilta-cel) and KarMMa-3 (ide-cel) trials. This updated MAIC includes longer follow-up and overall survival (OS).

Methods: An unanchored MAIC was performed utilizing individual patient-level data (IPD) from CARTITUDE-4 [1-3 prior lines of therapy (LOT); n = 208] and CARTITUDE-1 (3-4 prior LOT; n = 37). Patients fulfilling KarMMa-3 inclusion criteria (2-4 prior LOT, triple-class exposed) were selected, and outcomes were compared against published aggregate KarMMa-3 data. Cilta-cel IPD were weighted to match reported baseline characteristics of KarMMa-3 on key prognostic factors identified a priori. Comparative efficacy was estimated for progression-free survival (PFS), OS, overall response rate, very good partial response (VGPR) or better rate, and complete response (CR) or better rate.

Results: Eighty-five patients from CARTITUDE-4 and CARTITUDE-1 were included. After adjustment, patients in the cilta-cel group (effective sample size = 39) had a 58% reduction in PFS risk [hazard ratio (HR) 0.42 (95% CI 0.26-0.68); p = 0.0004] and a 42% reduction in OS risk [HR 0.58 (0.34-0.99); p = 0.0452] versus ide-cel. Patients in the cilta-cel group were significantly more likely to achieve an overall response [relative response ratio (RR) 1.22 (95% CI 1.08-1.38); p = 0.0126] and deeper levels of response [≥ VGPR: RR 1.37 (1.19-1.59); p = 0.0009; ≥ CR: RR 1.80 (1.49-2.18); p < 0.0001] versus ide-cel.

Conclusion: This updated MAIC with longer follow-up time demonstrated significant superiority of cilta-cel over ide-cel in PFS, OS, and response outcomes in patients with triple-class exposed RRMM treated with 2-4 prior LOT. The OS results reinforce the added value of cilta-cel in this population.

Trial registration: ClinicalTrials.gov ID: CARTITUDE-1: NCT03548207; CARTITUDE-4: NCT04181827; KarMMa-3: NCT03651128.

Keywords: CARTITUDE-1; CARTITUDE-4; Ciltacabtagene autoleucel; Comparative efficacy; Lenalidomide-refractory; Matching-adjusted indirect comparison; Overall survival; Relapsed or refractory multiple myeloma.

MeSH terms

  • Aged
  • Antigens, CD19* / therapeutic use
  • Female
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Male
  • Middle Aged
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / mortality
  • Multiple Myeloma* / therapy
  • Neoplasm Recurrence, Local
  • Receptors, Chimeric Antigen
  • Treatment Outcome

Substances

  • idecabtagene vicleucel
  • Antigens, CD19
  • Receptors, Chimeric Antigen

Associated data

  • ClinicalTrials.gov/NCT03548207
  • ClinicalTrials.gov/NCT04181827
  • ClinicalTrials.gov/NCT03651128