Poor outcomes with BCMA-targeting bispecific antibodies following early relapse from ide-cel: a real-world French study
Year: 2025
Type: article
Study design: Observational Study
Abstract: 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.
Source: Blood Advances
Authors: Sarah Cayla, Lionel Karlin, Jérôme Lambert, Anne Lazareth, Alexis Talbot, Mohamad Mohty, Florent Malard, Marie-Odile Petillon, Salomon Manier, Ibrahim Yakoub-Agha, Denis Caillot, Ingrid Lafon, Xavier Leleu, Niels Moya, Bruno Royer, Jean-Marc Schiano De Colella, Gabriel Brisou, Cyrille Touzeau, Aurore Perrot, Pierre Bories, Laure Vincent, Hanane Guedon, Olivier Decaux, Benoît Ferment, Roch Houot, Steven Le Gouill, Noémie Bigot, Thierry Facon, Jill Corre, Hervé Avet-Loiseau, Philippe Moreau, Bertrand Arnulf
Institutions: Assistance Publique – Hôpitaux de Paris, Hôpital Saint-Louis, Laboratoire d'hématologie, Hôpital Lyon Sud, Inserm, Institut de recherche Saint-Louis, Université Paris Cité, Sorbonne Université, Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine, Intergroupe Francophone du Myélome, Centre Hospitalier Universitaire de Lille, Institute for Translational Research in Inflammation, CHU Dijon Bourgogne, Laboratoire Interdisciplinaire Carnot de Bourgogne, Centre Hospitalier Universitaire de Poitiers, Institut Paoli-Calmettes, Centre Hospitalier Universitaire de Nantes, Centre Hospitalier Universitaire de Toulouse, Université de Toulouse, Institut universitaire du cancer de Toulouse Oncopole, Centre Hospitalier Universitaire de Montpellier, Hôpital Saint Eloi, Hôpital Pontchaillou, Centre Hospitalier Universitaire de Rennes, Institut Curie, Université de Lille, Nantes Université
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
OpenAlex ID: W4414319263