Poor outcomes with BCMA-targeting bispecific antibodies following early relapse from ide-cel: a real-world French study

Idecabtagene vicleucel (ide-cel), an adoptive chimeric antigen receptor T-cell therapy directed against B-cell maturation antigen (BCMA), has demonstrated high response rates and improved survival in patients with relapsed/refractory multiple myeloma. However, all patients eventually relapse, and data on salvage therapy outcomes remain limited. We conducted a national, real-world study of 154 patients relapsing after ide-cel, with a median time to progression of 6.0 months (interquartile range, 3.0-9.9). Salvage therapies included anti-BCMA bispecific antibodies (BsAbs) (n = 79), non-BCMA BsAbs targeting GPRC5D or FcRH5 (n = 12), combinations of immunomodulatory agent, proteasome inhibitor, and anti-CD38 monoclonal antibody (n = 40), and others (n = 23). Median overall survival (OS) was 12.12 months (95% confidence interval, 6.6 to not reached), and median progression-free survival (PFS) was 3.48 months (95% CI, 2.6-6.37). The overall response rate (≥ partial response) was higher in patients treated with BsAbs (36%) than others (13%, P = .002). Treatment with non-BCMA BsAbs resulted in significantly higher ORR (67% vs 30%, P = .018), OS (19.48 vs 8.41 months, P = .034) and PFS (9.2 vs 3.81 months, P = .035) compared to anti-BCMA BsAbs. Early relapse after ide-cel (≤6 months) was associated with worse outcomes (OS: 5.95 vs 12.58 months, P = .040), as was extramedullary disease (OS: 13.8 vs 6.28 months, P = .033) and exposure to >3 prior lines of therapy. In summary, anti-BCMA BsAbs offered limited efficacy whereas non-BCMA BsAbs may offer a promising therapeutic approach following ide-cel early relapse. These results underscore the potential benefits of diversifying targets in relapse post-ide-cel treatment strategies. This trial was registered at www.clinicaltrials.gov as #NCT04328298.

Authors

Institutions

Publication Details

Journal
Blood Advances
Published
2025-09-18
DOI
https://doi.org/10.1182/bloodadvances.2025017597
Citations
2
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
2.09

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Poor outcomes with BCMA-targeting bispecific antibodies following early relapse from ide-cel: a real-world French study

Gabriel Brisou, Marie‐Odile Petillon, Steven Le Gouill, Mohamad Mohty et al.
2 citations
Blood Advances
CAR-T cell therapy research
2.09
article

Poor outcomes with BCMA-targeting bispecific antibodies following early relapse from ide-cel: a real-world French study

Gabriel Brisou, Marie‐Odile Petillon, Steven Le Gouill, Mohamad Mohty, Pierre Bories, Thierry T.F. Facon, Benoît Ferment, Bertrand Arnulf, Jill Corre, Roch Houot, Niels Moya, Salomon Manier, Anne Lazareth, Lionel Karlin, Jérôme Lambert, Xavier P Leleu, Ibrahim Yakoub‐Agha, Florent Malard, Jean‐Marc Schiano de Colella, Cyrille Touzeau, Hanane Guedon, Hervé Avet‐Loiseau, Alexis Talbot, Denis Caillot, Laure Vincent, Bruno Royer, Aurore Perrot, Ingrid Lafon, Sarah Cayla, Philippe Moreau, Noémie Bigot, Olivier Decaux
article en
2 citations

Abstract

Idecabtagene vicleucel (ide-cel), an adoptive chimeric antigen receptor T-cell therapy directed against B-cell maturation antigen (BCMA), has demonstrated high response rates and improved survival in patients with relapsed/refractory multiple myeloma. However, all patients eventually relapse, and data on salvage therapy outcomes remain limited. We conducted a national, real-world study of 154 patients relapsing after ide-cel, with a median time to progression of 6.0 months (interquartile range, 3.0-9.9). Salvage therapies included anti-BCMA bispecific antibodies (BsAbs) (n = 79), non-BCMA BsAbs targeting GPRC5D or FcRH5 (n = 12), combinations of immunomodulatory agent, proteasome inhibitor, and anti-CD38 monoclonal antibody (n = 40), and others (n = 23). Median overall survival (OS) was 12.12 months (95% confidence interval, 6.6 to not reached), and median progression-free survival (PFS) was 3.48 months (95% CI, 2.6-6.37). The overall response rate (≥ partial response) was higher in patients treated with BsAbs (36%) than others (13%, P = .002). Treatment with non-BCMA BsAbs resulted in significantly higher ORR (67% vs 30%, P = .018), OS (19.48 vs 8.41 months, P = .034) and PFS (9.2 vs 3.81 months, P = .035) compared to anti-BCMA BsAbs. Early relapse after ide-cel (≤6 months) was associated with worse outcomes (OS: 5.95 vs 12.58 months, P = .040), as was extramedullary disease (OS: 13.8 vs 6.28 months, P = .033) and exposure to >3 prior lines of therapy. In summary, anti-BCMA BsAbs offered limited efficacy whereas non-BCMA BsAbs may offer a promising therapeutic approach following ide-cel early relapse. These results underscore the potential benefits of diversifying targets in relapse post-ide-cel treatment strategies. This trial was registered at www.clinicaltrials.gov as #NCT04328298.

Blood AdvancesVol. 10(4)
Inserm (FR), Université Fédérale de Toulouse Midi-Pyrénées (FR), Université Paris Cité (FR), Université de Lille (FR), Saint Louis University Hospital (US), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nantes (FR), Sorbonne Université (FR), Sorbonne Paris Cité (FR), Centre Hospitalier Universitaire de Montpellier (FR), Assistance Publique – Hôpitaux de Paris (FR), Institut universitaire du cancer de Toulouse Oncopole (FR), Hôpital Saint-Antoine (FR), Centre Hospitalier Universitaire de Poitiers (FR), Institut de Cancérologie de Bourgogne (FR), Hôpital Lyon Sud (FR), CHU Dijon Bourgogne (FR), Intergroupe Francophone du Myélome (FR), Centre de Recherche Saint-Antoine (FR), Hôpital Saint Eloi (FR), Hôpital Saint-Louis (FR), Institut Paoli-Calmettes (FR), Laboratoire de Génétique Cellulaire (FR), Centre Hospitalier Universitaire de Rennes (FR), Institut Curie (FR)
Amgen, Bristol-Myers Squibb, Pfizer, AstraZeneca, Sanofi, Gilead Sciences, Celgene, Therakos, Adaptive Biotechnologies, BeiGene, Incyte, Astellas Pharma, Servier
Openalex Percentile: Top 10%
CAR-T cell therapy research
2.09
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.