CAR T-cells or bispecific antibodies for relapsed/refractory multiple myeloma: Head-to-head real-world european comparison
Year: 2025
Type: conference-abstract
Abstract: Background: BCMA-directed CAR-T therapies and bispecific antibodies (BsAbs) have transformed the treatment landscape for relapsed/refractory multiple myeloma (RRMM), yet the optimal sequencing of these therapies remains unclear. Limited access to CAR-T – especially across Europe – and the lack of direct comparative data hinder clinical decision-making. To address this, we conducted a large, real-world, multicenter European study using propensity-weighted analysis to compare the efficacy, safety, and accessibility of CAR-T versus BsAb therapy in RRMM. Methods: We retrospectively analyzed 640 patients with RRMM treated with either a BCMA-directed CAR-T product (n=399; including idecabtagene vicleucel [ide-cel], ciltacabtagene autoleucel [cilta-cel], and academic CAR-T construct [ARI]) or a BsAb (n=241; including teclistamab, talquetamab, and elranatamab). Among BsAb-treated patients, 200 had no access to CAR-T due to regulatory, logistical, or economic barriers. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline differences in key prognostic covariates: extramedullary disease (EMD), high-risk cytogenetics, International Staging System (ISS), ECOG performance status, penta-refractoriness, and age. The co-primary endpoints were overall response rate (ORR) and progression-free survival (PFS), assessed by Kaplan-Meier analysis and IPTW-adjusted Cox proportional hazards regression. Safety endpoints were immune effector cell associated neurotoxicity (ICANS), cytokine release syndrome (CRS), and non-relapse mortality (NRM). Results: Patients treated with BsAb were generally older (median age 66 vs. 64 years) and exhibited a higher burden of adverse clinical features compared to those receiving CAR-T therapy. Specifically, high-risk cytogenetics (74% vs. 55%), extramedullary disease (EMD, 32% vs. 25%), and ECOG performance status ≥2 (35% vs. 17%) were more prevalent in the BsAb cohort. The ORR was significantly higher among CAR-T recipients (p<0.001), with complete response rates reaching 58% in the CAR-T group versus 15% in BsAb-treated patients. Among CAR-T products, cilta-cel achieved the highest complete response rate (69%), followed by academic CAR-T (ARI, 60%) and ide-cel (48%). In contrast, BsAbs showed markedly lower CR rates: elranatamab (22%), teclistamab (17%), and talquetamab (9%). At a median follow-up of 12 months, PFS consistently favored CAR-T over BsAb treatment. Unadjusted 12-month PFS was 66% in the CAR-T group compared to 47% for BsAbs. This benefit was maintained across subgroups stratified by EMD status: among EMD-negative patients, 12-month PFS was 70% (CAR-T) vs. 54% (BsAb), and for EMD-positive patients, 52% vs. 32%, respectively. Product-level analysis highlighted cilta-cel with the highest PFS at 86%, followed by ARI (69%) and ide-cel (52%). Among BsAbs, teclistamab and elranatamab showed comparable PFS rates of 44% and 46%. In IPTW-adjusted Cox regression, BsAb therapy remained significantly associated with shorter PFS (HR 1.54; 95% CI: 1.13-2.10; p=0.006). EMD (HR 2.03; 95% CI: 1.43-2.87; p<0.001) and ECOG ≥2 (HR range: 2.08-2.66; p<0.02) were identified as strong independent predictors of inferior PFS, while age and high-risk cytogenetics showed attenuated effects after adjustment. Safety profiles differed notably between modalities. BsAbs were generally better tolerated, with lower incidences of CRS and ICANS compared to cilta-cel and ide-cel. ARI showed similarly low toxicity to BsAbs. However, NRM varied significantly across agents (p=0.005): NRM was 5% for ide-cel, 6% for both cilta-cel and ARI, but higher in BsAb recipients – 12% for teclistamab, 11% for talquetamab, and notably 20% for elranatamab Conclusion: This is the first large-scale, real-world comparative analysis of BCMA-targeted CAR-T versus BsAb therapies in RRMM across European countries, adjusted for both access disparities and baseline prognostic factors. Cilta-cel and ARI demonstrated superior PFS compared to BsAbs, while ide-cel performed comparably to BsAb therapies. In settings where access to commercial CAR-Ts is limited or absent, academic CAR-T approaches must match the efficacy of cilta-cel to offer a meaningful advantage over readily available off-the-shelf BsAbs. These data underscore the importance of both innovation and equitable access in determining treatment sequencing strategies in RRMM.
Source: Blood
Authors: Maximilian Merz, Tomas Jelinek, Thomas Pabst, Raphael Teipel, Anca-Maria Albici, Bastian von Tresckow, Marcel Teichert, Uta Demel, Antonia Busse, Marie Wesener, Tobias A.W. Holderried, Friederike Schmitz, Fabian Müller, Friedrich-Linus Roessiger, Barbara Jeker, Michele Hoffmann, Natalie Schub, Natalia Tovar, Ben-Niklas Baermann, Stork Martin, Alexandra Jungova, Jiri Minarik, Jakub Radocha, Ivan Špička, Ludek Pour, Polona Novak, Klara Slajpah, Karla Rener, Matjaz Sever, Ulrich Keller, Stephan Bohl, Francis Ayuk, David Fandrei, Patrick Born, Vladan Vucinic, Nicolaus Kroeger, Irene Strassl, Friedrich Stoelzel, Roman Hajek, Carlos Fernandez de Larrea, Nico Gagelmann
Institutions: Memorial Sloan Kettering Cancer Center, University of Ostrava, University Hospital of Bern, University Hospital Schleswig-Holstein, Charité - Universitätsmedizin Berlin, Friedrich-Alexander-Universität Erlangen-Nürnberg, Hospital Clínic de Barcelona, Palacký University Olomouc, University Hospital Hradec Králové, Ljubljana University Medical Centre, University Medical Center Hamburg-Eppendorf, University Hospital Leipzig
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417019671
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