P-304: TRIPLE CLASS REFRACTORY MULTIPLE MYELOMA: EFICACY OF THE NEW IMMUNOTHERAPIES AND NEW UNMET MEDICAL NEED

Introduction: The prognosis of triple class refractory (TCR) multiple myeloma (MM) patients is dismal, mainly due to the lack of rescue therapies. Newer immunotherapy approaches such us chimeric antigen receptor T (CAR-T) cells and bispecific monoclonal antibodies (BiAbs) directed against BCMA, GPRC5D or FcRH5 have been effective in the TCR setting. However, there are not studies that compared the effectiveness of CAR-T and BiAbs, as well as which is the prognosis of patients who relapsed to these treatments.

Methods: An observational retrospective study was conducted to indirectly compare the efficacy of CAR-T and BiAbs in 68 TCR patients treated within clinical trials between December 2018 and February 2023.

Results: Sixty-eight patients were included in this study, 31 were treated with CAR-T and 37 with BiABs (directed against BCMA in 23, GPRC5D in 11 and FcRH5 in 3 patients). No differences were observed except that the BiAbs group had higher proportion of patients >65 years, with more extramedullary disease at relapse and more pretreated compared to the CAR-T group.
The overall rate response (at least partial response) was significantly better in the CAR-T group than the BiAbs group (odds ratio 22.1 [95% confidence interval (CI), 2.7-179.9]; P=0.004). In addition, patients treated with CAR-T reached more frequently complete response or better (66.7% vs. 43.2%; P=0,056).
After a median of follow-up of 14.6 months (m) (interquartile range, 3,7-54,1), no differences in the progression-free survival (PFS) were observed between the CAR-T and the BiAbs groups (14.1 vs. 12,1 m; P=0.110), but patients receiving CAR-T achieved longer overall survival (OS) (43.0 vs. 18.2 m, hazard ratio 2.3 [95% CI, 1.1-5.2]; P=0.050).
Thirty-two patients (12 in the CAR-T and 20 in the BiAbs group) were rescued after progression. Overall, these rescue therapies were very heterogeneous, but 66.7% of the CAR-T group and 25% of the BiAbs group were treated with BiAbs in the subsequent treatment. Patients treated with BiAbs at relapsed showed a trend toward better response. Patients in the CAR-T group who were treated with BiAbs (with a different target than the BCMA) presented the longest PFS 2 (29.1 m), significantly more prolonged than patients in this group rescued with other schemes, (7,9 m, P< 0.001), as well as patients of the BiAbs group regardless of the treatment used at relapse (BiAbs: 7,3 m, P< 0.001; and other therapies: 8.4 m, P=0.002).

Conclusions: The present study showed that CAR-T and BiAbs are effective treatment in TCR MM patients. In this scenario, CAR-T resulted in better responses, but no differences were observed in PFS compared to BiAbs. However, patients of the CAR-T group presented superior OS showing the importance of treatment sequence and how BiAbs could be useful after CAR-T to improve survival in TCR patients. The identification of sequence approach as well as the development of novel drugs represent the new unmet medical need in the relapse of patients TCR after the new immunotherapy.