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

Date publication

septembre 2025

Journal

Blood advances

Auteurs

Membres identifiés du Cancéropôle Est :
Dr CAILLOT Denis

Tous les auteurs :
Cayla S, Karlin L, Lambert J, Lazareth A, Talbot A, Mohty M, Malard F, Petillon MO, Manier S, Yakoub-Agha I, Caillot D, Lafon I, Leleu X, Moya N, Royer B, Schiano de Colella JM, Brisou G, Touzeau C, Perrot A, Bories P, Vincent L, Guedon H, Decaux O, Ferment B, Houot R, Le Gouill S, Bigot N, Facon T, Corre J, Avet-Loiseau H, Moreau P, Arnulf B

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/40966637

Résumé

Idecabtagene vicleucel (ide-cel), an adoptive chimeric antigen receptor (CAR) 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 [IQR], 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%CI, 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 (ORR) (≥ partial response) was higher in patients treated with BsAbs (36%) than others (13%, p=0.002). Treatment with non-BCMA BsAbs resulted in significantly higher ORR (67% vs. 30%, p=0.018), OS (19.48 vs. 8.41 months, p=0.034) and PFS (9.2 vs. 3.81 months, p=0.035) 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=0.040), as was extramedullary disease (OS: 13.8 vs 6.28 months, p=0.033) 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. ClinicalTrials.gov identifier NCT04328298.

Référence

Blood Adv. 2025 09 18;: