BACKGROUND: Targeted immunotherapies have brought about remarkable advancements in the treatment of multiple myeloma (MM), particularly through the rise of chimeric antigen receptor T cells (CAR T) and bispecific T-cell engagers (TCEs). GPRC5D (G-protein–coupled receptor class C group 5 member D) and BCMA (B-cell maturation antigen) have become key targets for various therapies, including CAR T-cell treatments, bispecific antibodies, and antibody-drug conjugates (ADC). Recently approved therapies targeting BCMA and GPRC5D have produced extraordinary results in patients with triple-class exposure, who would otherwise face significantly poor overall survival rates. However, there is still limited data available on optimal sequencing BCMA and GPRC5D agents to support informed decision-making.

METHODS: The BiTAL study is an ongoing, retrospective, observational study with patient data collected from 68 centers across Spain, covering a chart review period from September 2024 to May 2025. The study included adult patients with TCE RRMM who began TAL monotherapy under the pre-approval access programs between November 2022 and November 2024. TAL was administered in a weekly or biweekly (Q2W) schedule, following TAL SmPC. Here we present a programmed subgroup analysis to investigate the outcomes of talquetamab (TAL) therapy on both BCMA exposed and BCMA-naïve patients.

RESULTS: Among 163 patients in the evaluable population at the data cut-off date (May 12th, 2025), 147 had sufficient data for analysis—52 were classified as BCMA exposed and 95 as BCMA naïve. Within the BCMA exposed group, 41 patients received belantamab, 6 were treated with a BCMA-bispecific antibody, and 5 received BCMA-CAR T. The median time to next treatment of BCMA-exposed patients from BCMA agent to TAL was 4.4 months (CI95% 3.1-5.1): 5 patients BCMA-CART 10.9 months (CI95% 3.5-18.2), 30 patients belantamab 3.9 months (CI95% 3-5) and 5 patients BCMA-BsA 4.9 months (CI95% 2.1-7.7). The majority of patients received TAL every two weeks, at rates of 90% and 86%, BCMA exposed and naïve, respectively. The baseline characteristics analyzed showed a generally good balance between the groups; however, statistically significant differences were noted in the median time from diagnosis, 7 years (range 1.2-25.3) for the BCMA exposed group and 4.5 years (range 0.7-23.2) for the BCMA naïve group (U Mann-Whitney test p-value: 0.001). The median number of prior treatment lines was also different, at 5 (range 2-9) for BCMA exposed patients and 3 (range 1-8) for BCMA naïve patients (U Mann-Whitney test p-value: <0.001). No significant differences were found regarding triple or penta-exposure/refractoriness. The overall response rates and complete response rates were 89% (39/44) and 28% (12/44) for BCMA exposed patients, and of 81% (70/86) and 24% (21/86) for BCMA naïve patients. With a median follow-up of 12.6 months (range 0.1-24) for the BCMA exposed group and 10.3 months (range 0.1-26.2) for the BCMA naïve group, no statistically significant differences were found in progression-free survival (PFS) or overall survival (OS). The median PFS was 9.9 months (95% CI: 5.49-14.22) for the BCMA exposed group and 8.4 months (95% CI: 4.6-12.22) for the BCMA naïve group (Log-rank test p-value: 0.681). The median OS was not estimable for the BCMA exposed group and was 20 months (95% CI: 14.9-25.1) for the BCMA naïve group (Log-rank test p-value: 0.833). More information on effectiveness will be provided for presentation at the congress.CONCLUSIONS: Our study on TAL therapy in a setting comparable to real-world conditions, highlighted noteworthy response rates and survival among both BCMA exposed and naïve groups, though no significant differences in progression-free survival or overall survival were observed. These findings underscore the potential of TAL in treating BCMA-exposed patients, even though the majority were treated with BCMA ADC. While the retrospective nature of this study imposes some limitations, these insights may be valuable for improving clinical decision-making.

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2025
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