Bispecific antibodies targeting BCMA or GPRC5D are highly effective in relapsed myeloma after CAR T-cell therapy

Merz M, Dima D, Hashmi H, Ahmed N, Stölzel F, Holderried TA, Fenk R, Müller F, Tovar N, Oliver-Cáldes A, Rathje K, Davis JA, Fandrei D, Vucinic V, Kharboutli S, Baermann BN, Ayuk F, Platzbecker U, Albici AM, Schub N, Schmitz F, Shune L, Khouri J, Anwer F, Raza S, McGuirk J, Mahmoudjafari Z, Green K, Khandanpour C, Teichert M, Jeker B, Hoffmann M, Kröger N, von Tresckow B, de Larrea CF, Pabst T, Abdallah AO, Gagelmann N (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Blood Cancer Journal Nature Publishing Group / Nature Publishing Group: Open Access Journals - Option B

Book Volume: 14

Article Number: 214

Journal Issue: 1

DOI: 10.1038/s41408-024-01197-2

Abstract

Despite the astonishing outcomes after chimeric antigen receptor (CAR) T-cell therapy for relapsed refractory multiple myeloma (RRMM), most patients eventually relapse. There are only limited data available on salvage therapies following relapse after BCMA-directed CAR T-cell therapy. Here, we analyzed outcomes of post-CAR T-cell therapy relapse and impact of different salvage strategies in an international cohort of 139 patients (n = 130 ide-cel, n = 9 cilta-cel), receiving talquetamab (n = 28), teclistamab (n = 37), combinations of immunomodulating drugs (IMiDs), proteasome inhibitors (PIs) or CD38 monoclonal antibodies (n = 43), and others (n = 31). The median time to relapse after CAR T-cell therapy was 5 months, 53% had the extramedullary disease (EMD) at relapse, associated with dismal post-relapse outcome (P = 0.005). Overall response and complete response upon salvage therapies were 79% and 39% for talquetamab, 64% and 32% for teclistamab, 30% and 0% for IMiDs/PIs/CD38, and 26% and 3% for others (P < 0.001). Duration of response, as well as median survival, was significantly improved with bispecific antibodies (P < 0.001, respectively). Bispecific antibodies seemed to overcome the poor prognosis associated with early relapse and EMD, and were independent predictors for improved survival in multivariable analysis. In summary, these results suggest bispecific antibodies as the standard of care for relapse after CAR T-cell therapy for RRMM.

Authors with CRIS profile

Fabian Müller Department of Medicine 5 – Haematology and Oncology

Involved external institutions

Inselspital, Universitätsspital Bern CH Switzerland (CH) US Myeloma Innovations Research Collaborative (USMIRC) US United States (USA) (US) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Cleveland Clinic US United States (USA) (US) Universitätsklinikum Essen DE Germany (DE) Hospital Clínic de Barcelona ES Spain (ES) Universität zu Lübeck DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Universitätsklinikum Leipzig DE Germany (DE) Universitätsklinikum Bonn DE Germany (DE) Universitätsklinikum Düsseldorf DE Germany (DE)

How to cite

APA:

Merz, M., Dima, D., Hashmi, H., Ahmed, N., Stölzel, F., Holderried, T.A.,... Gagelmann, N. (2024). Bispecific antibodies targeting BCMA or GPRC5D are highly effective in relapsed myeloma after CAR T-cell therapy. Blood Cancer Journal, 14(1). https://doi.org/10.1038/s41408-024-01197-2

MLA:

Merz, Maximilian, et al. "Bispecific antibodies targeting BCMA or GPRC5D are highly effective in relapsed myeloma after CAR T-cell therapy." Blood Cancer Journal 14.1 (2024).

BibTeX: Download