Introduction: Survival rates for patients with multiple myeloma (MM) have recently improved, thanks to an increase in treatment options targeting receptors such as B-cell maturation antigen (BCMA). However, this introduces a new population of patients with refractoriness to both standard-of-care and novel BCMA therapies, limiting treatment options. Therefore, understanding real-world outcomes of BCMA-exposed patients is essential.

Methods: Data from three European MM registries were included: IUCT (France), RMG (Czech Republic), and TriNetX (Germany). Eligible patients had previously received PI, IMID, anti-CD38 and anti-BCMA therapy between 2020 and 2024. Patients receiving re-treatment with anti-BCMA immunotherapy were excluded from this publication. Locally collected patient-level data were analyzed uniformly, and site-specific results were aggregated centrally using the HONEUR federated data network. Patient characteristics and treatment patterns were descriptively analyzed. Index date was considered as the date of initiating the subsequent therapy after anti-BCMA treatment. Time to next treatment (TTNT), as a proxy for progression-free survival, and overall survival (OS) were assessed using Kaplan-Meier and proportional hazards regression. The Last Observation Carried Forward (LOCF) method was employed for the International Staging System (ISS) and cytogenetics data.

Results: A total of 185 patients who had received an anti-BCMA-based regimen were analyzed from three European registries. Most cases came from IUTC (76.8%), with RMG contributing to 9.7% and TriNetX contributing to 13.5% of cases.

Baseline characteristics revealed that 32.4% of patients were younger than 65 years old, 44.9% were 65 to 74 years old, and 22.7% were ≥75 years of age. Forty-seven percent of patients were ISS stage II or III, and 22.7% presented with high-risk cytogenetics, defined as any presence of del(17p) and/or t(4;14) and/or t(14;16). Most patients (69.2%) had previously undergone autologous stem cell transplantation (ASCT). With a median of 5 prior lines of treatment, only 22.7% of patients received 3 or 4 prior lines of treatment. Regarding refractoriness, 90.3% of patients were triple-class refractory and 55.1% were penta-drug refractory, highlighting the significant treatment resistance within this relapsed/refractory MM population observed in real-world clinical practice. Despite 23.2% of missing data on subsequent therapies following BCMA exposure, the available treatment regimens predominantly included chemotherapy doublet (30.8%), IMID/PI based triplet (16.8%), IMID/PI based doublet (11.4%), and 5.4% anti-CD38 based triplet.

With a median follow-up of 10 months, efficacy data revealed that median TTNT was 5.2 months (95% CI: 3.71 to 6.24 months) and median OS was 12.5 months (95% CI: 9.00 to 23.06 months).

Conclusions: Advances such as anti-BCMA therapy still reveal a treatment gap in heavily pre-treated patients. The continued reliance mainly on chemotherapy and IMID/PI triplets as subsequent treatment indicates a critical gap in therapy development and the necessity for new therapeutic targets to be adopted in clinical practice.

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2025
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