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Introduction <p>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).</p> Methods <p>An unanchored MAIC was performed utilizing individual patient-level data (IPD) from CARTITUDE-4 [1–3 prior lines of therapy (LOT); <i>n</i> = 208] and CARTITUDE-1 (3–4 prior LOT; <i>n</i> = 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.</p> Results <p>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); <i>p</i> = 0.0004] and a 42% reduction in OS risk [HR 0.58 (0.34–0.99); <i>p</i> = 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); <i>p</i> = 0.0126] and deeper levels of response [≥ VGPR: RR 1.37 (1.19–1.59); <i>p</i> = 0.0009; ≥ CR: RR 1.80 (1.49–2.18); <i>p</i> &lt; 0.0001] versus ide-cel.</p> Conclusion <p>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.</p> Trial Registration <p>ClinicalTrials.gov ID: CARTITUDE-1: NCT03548207; CARTITUDE-4: NCT04181827; KarMMa-3: NCT03651128.</p>

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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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月2日

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  • Nieves Lopez-Muñoz,
  • Noffar Bar,
  • Joris Diels,
  • Suzy van Sanden,
  • João Mendes,
  • Seina Lee,
  • Teresa Hernando,
  • Nikoletta Lendvai,
  • Nitin Patel,
  • Tadao Ishida,
  • Jeremy Er,
  • Simon J. Harrison

摘要

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.