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Randomized Controlled Trial
. 2025 Jul;42(7):3223-3239.
doi: 10.1007/s12325-025-03205-8. Epub 2025 May 12.

Comparative Efficacy of Ciltacabtagene Autoleucel Versus Standard-of-Care Treatments for Patients with Previously Treated Relapsed or Refractory Multiple Myeloma: A Matching-Adjusted Indirect Comparison

Noemi Puig  1 , Joris Diels  2 , Suzy van Sanden  2 , João Mendes  3   4 , Heather Burnett  5 , Allie Cichewicz  5 , Seina Lee  6 , Teresa Hernando  7 , Jordan M Schecter  8 , Nikoletta Lendvai  8 , Nitin Patel  9 , José María Sanchez-Pina  10 , Serena Rocchi  11 , Roberto Mina  12 , Paolo Corradini  13 , Michele Cavo  14 , Jesús San Miguel  15 , Leyla Shune  16 , Abdullah M Khan  17 , Surbhi Sidana  18 , Xavier Leleu  19 , Salomon Manier  20 , Brea Lipe  21 , Katja Weisel  22 , Joaquin Martinez-Lopez  23
Affiliations
Randomized Controlled Trial

Comparative Efficacy of Ciltacabtagene Autoleucel Versus Standard-of-Care Treatments for Patients with Previously Treated Relapsed or Refractory Multiple Myeloma: A Matching-Adjusted Indirect Comparison

Noemi Puig et al. Adv Ther. 2025 Jul.

Abstract

Introduction: Matching adjusted indirect comparisons (MAICs) were performed to compare the efficacy of cilta-cel versus elotuzumab + pomalidomide + dexamethasone (EloPd), isatuximab + carfilzomib + dexamethasone (IsaKd), isatuximab + pomalidomide + dexamethasone (IsaPd), and selinexor + bortezomib + dexamethasone (SVd) in patients with relapsed or refractory multiple myeloma (RRMM) who have received at least one prior therapy and are lenalidomide-refractory.

Methods: Unanchored MAICs were performed using individual patient-level data (IPD) for all apheresed patients randomized to the cilta-cel arm of CARTITUDE-4 (n = 208) and published arm-level data for EloPd from ELOQUENT-3 (n = 60), IsaKd from IKEMA (lenalidomide-refractory subgroup, n = 57), IsaPd from ICARIA-MM (n = 154), and SVd from BOSTON (lenalidomide-refractory subgroup, n = 53). Eligibility criteria from each comparator trial were applied to the cilta-cel arm IPD, and further imbalances in patient characteristics were adjusted by weighting the cilta-cel patient data to match the reported baseline characteristics of the comparator trials. Comparative efficacy was estimated for overall response rate, very good partial response or better (≥ VGPR) rate, complete response or better (≥ CR) rate, progression-free survival (PFS), and overall survival (OS).

Results: After adjustment, cilta-cel patients were significantly more likely to achieve an overall response versus EloPd, IsaPd, and SVd, and were significantly more likely to achieve ≥ VGPR and ≥ CR versus all comparators. Cilta-cel patients also had significant reductions in the risk of disease progression or death (PFS) versus all comparators: 64% versus EloPd, 49% versus IsaKd, 69% versus IsaPd, and 62% versus SVd. Similarly, cilta-cel patients had significant improvements in OS for all feasible comparisons: 52% versus EloPd, 58% versus IsaPd, and 60% versus SVd.

Conclusion: Cilta-cel patients demonstrated clinically meaningful benefits over EloPd, IsaKd, IsaPd, and SVd for response and survival outcomes, highlighting its superiority over alternative treatment options for patients with RRMM who have received at least one prior therapy and are refractory to lenalidomide.

Keywords: Ciltacabtagene autoleucel; Matching-adjusted indirect comparison; Multiple myeloma.

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Conflict of interest statement

Declarations. Conflict of Interest: Noemi Puig: Amgen: Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; The Binding Site: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau. Joris Diels, Suzy van Sanden, João Mendes, Seina Lee, Teresa Hernando, Jordan M. Schecter, and Nikoletta Lendvai: Employees of Janssen and shareholders of Johnson & Johnson. Nitin Patel: Employee and shareholder of Legend Biotech USA Inc., has divested equity with BMS (via spouse). Heather Burnett and Allie Cichewicz: Employees of Evidera, a Thermo Fisher Company which provides consulting and other research services to life science companies. In their salaried positions, they work with a variety of companies and is precluded from receiving payment or honoraria directly from these organizations for services rendered. Evidera received payment from Johnson & Johnson for the conduct of this study. José María Sanchez-Pina: Consultancy and Speakers Bureau Johnson and Johnson, Gilead, Amgen, SanofiSerena Rocchi: Nothing to disclose. Roberto Mina: Received honoraria from AbbVie, Amgen, Bristol Myers Squibb, Celgene, GSK, Janssen, Sanofi, Takeda, Menarini Stemline and Pfizer; participated in advisory boards for Amgen, Bristol Myers Squibb, GSK, Janssen, Sanofi and Pfizer. Paolo Corradini: Honoraria and travel received from: Abbvie, Amgen, BeiGene, BMS, Eli Lilly, Gilead/Kite, GSK, Incyte, Janssen, Jazz Pharma, Novartis, Pfizer, Roche, Sanofi, SOBI, Takeda. Michele Cavo: Served as a consultant and received travel grants from Janssen. Jesus San Miguel: declares participation on advisory boards and consulting services, on behalf of my Institution, for Abbvie, Amgen, BMS, Celgene, GSK, Haemalogix, Janssen-Cilag, Karyopharm, MSD, Novartis, Pfizer, Takeda, Regeneron, Roche, Sanofi, SecuraBio and Gilead-Kite. Leyla Shune: serves as on J&J advisory boards. Abdullah M. Khan: Received research funding from BMS and Sanofi; member of the Speakers Bureau for Amgen, BMS, and Sanofi. Surbhi Sidana: Has received Research Funding: Magenta Therapeutics, BMS, Allogene, Janssen, Novartis and serves as a consultant for: Magenta Therapeutics, BMS, Janssen, Sanofi, Takeda, Regeneron, Abbvie, Pfizer, BiolineRx, Legend, Genentech, Arcellx, Kite. Xavier Leleu: Kite, A Gilead Company: Consultancy, Honoraria. Salomon Manier: Research funding Janssen, Celgene/BMS; Consultant for Abbvie, Adaptive Biotechnology, Amgen, Celgene/BMS, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda; Travel funding: Abbvie, Adaptive Biotechnology, Amgen, Celgene/BMS, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Roche, Sanofi. Brea Lipe: Consulting: Janssen, Sanofi, Karyopharm, BMS, Pfizer, GSK and Research: Amgen, Karyopharm. Katja Weisel: Research Grant: Abbvie, Amgen, BMS/Celgene, GSK, Janssen, Sanofi (to the Institution). Honoraria: Abbvie, Amgen, Adaptive Biotech, Astra Zeneca, Beigene, BMS, Celgene, Janssen, GSK, Karyopharm, Menarini, Novartis, Oncopeptides, Pfizer, Roche, Sanofi, Stemline, Takeda; Adisory Board: Abbvie, Amgen, Adaptive Biotech, Beigene, BMS, Celgene, Janssen, GSK, Karyopharm, Menarini, Novartis, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Takeda. Joaquin Martinez-Lopez: has stock ownership in altum, statb therapeutics; has received honorarium from Johnson and Johnson, BMS, Pfizer, Incity, Roche, Sanofi, Novartis; has served as a consultant for Johnson and Johnson, BMS, Pfizer, Incity, Roche, Sanofi, Novartis; has served on Speaker’s Bureau for Johnson and Johnson, BMS, Pfizer, Incity, Roche, Sanofi, Novartis, Amgen; has research funding from BMS, J&J, Incity, Pfizer, Amgen and travel funds from Johnson and Johnson, BMS, Pfizer, Incity, Roche, Sanofi, Novartis. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. This analysis utilized de-identified data from published clinical trial data and therefore ethics committee approval was not required. Each individual trial included in this analysis was approved by independent ethics committees or institutional review boards at each study site and all patients provided written informed consent before enrolling in each clinical trial. Study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments.

Figures

Fig. 1
Fig. 1
Observed and adjusted Kaplan–Meier plots of PFS for cilta-cel versus EloPd (a), IsaKd (b), IsaPd (c), and SVd (d). Dark green denotes values for cilta-cel observed, light green cilta-cel adjusted, and blue each comparator. CI confidence interval, EloPd elotuzumab, pomalidomide, dexamethasone, ESS effective sample size, HR hazard ratio, IsaKd isatuximab, carfilzomib, dexamethasone, IsaPd isatuximab, pomalidomide, dexamethasone, LOT line of therapy, NA not assessed, SVd selinexor, bortezomib, dexamethasone
Fig. 2
Fig. 2
Observed and adjusted Kaplan–Meier plots of OS for cilta-cel versus EloPd (a), IsaPd (b), and SVd (c). Dark green denotes values for cilta-cel observed, light green cilta-cel adjusted, and blue each comparator. CI confidence interval, EloPd elotuzumab, pomalidomide, dexamethasone, ESS effective sample size, HR hazard ratio, IsaPd isatuximab, pomalidomide, dexamethasone, LOT line of therapy, NA not assessed, SVd selinexor, bortezomib, dexamethasone
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References

    1. Du J, Zhuang J. Major advances in the treatment of multiple myeloma in American Society of Hematology annual meeting 2020. Chronic Dis Transl Med. 2021;7(4):220–6. - PMC - PubMed
    1. Yang Q, Li X, Zhang F, et al. Efficacy and safety of CAR-T therapy for relapse or refractory multiple myeloma: a systematic review and meta-analysis. Int J Med Sci. 2021;18(8):1786–97. - PMC - PubMed
    1. Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328–46. - PubMed
    1. Avet-Loiseau H, et al. Poster EP1008 Treatment patterns of lenalidomide delivery and outcomes in multiple myeloma patients in real-world settings: a multi-center retrospective study. 25th Annual EHA Congress; June 11–21, 2020; Virtual2020.
    1. Hajek et al. 3204 Patient characteristics and survival outcomes of lenalidomide exposed non-refractory vs. lenalidomide refractory multiple myeloma patients in the HONEUR federated data network. 64th American Society of Hematology Annual Meeting and Exposition 2022 (ASH 2022); 10–13 December 2022; New Orleans, Louisiana2022.

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