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Outcomes in frail patients receiving BCMA-directed BsAbs for RRMM: A retrospective study
Elderly and frail patients with multiple myeloma (MM) have traditionally been excluded from clinical trials due to concerns around excessive toxicities, although real-world studies have demonstrated that increasing age and frailty should not be a barrier to effective MM treatments such as autologous stem cell transplantation and chimeric antigen receptor T-cell therapy. However, there is limited real-world evidence on bispecific antibodies for relapsed/refractory (R/R) MM. Adegbite et al. published a retrospective analysis in Blood Advances, assessing the impact of frailty on outcomes in 102 patients with RRMM treated with B-cell maturation antigen-directed bispecific antibodies between December 2017 and August 2024 at Memorial Sloan Kettering Cancer Center.1 Frailty was defined using the simplified frailty index based on age, Eastern Cooperative Oncology Group performance status, and Charlson comorbidity index, and cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, treatment-related mortality, overall response rates, progression-free survival, and overall survival were among the key endpoints.
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Key learnings |
| Rates of all grades of CRS (58% vs 60%; p = 0.99), ICANS (15% vs 8%; p = 0.44), and TRM (13% vs 21%; p = 0.27) were comparable between the frail vs non-frail group; rates of Grade ≥3 ICANS were also similar (3% vs 0%; p = 0.82). |
| Neither best ORR (80% vs 73%; p = 0.40), median PFS (NR vs 11 months; HR, 0.50; p = 0.051), nor median OS (37 months vs 25 months; p = 0.37) were significantly different between the frail vs non-frail groups, at a median follow-up of 8.6 months. |
| Patients with no prior anti-BCMA therapy had an improved PFS compared with those treated with prior anti-BCMA therapy (17 months vs 8 months; HR, 0.48; p = 0.016). |
| The findings support the use of BsAb as a treatment option for older and frail patients with RRMM, although age, comorbidities, and ECOG PS should be taken into account and optimized when assessing such patients for therapy. |
BCMA, B-cell maturation antigen; BsAb, bispecific antibody; CRS, cytokine release syndrome; ECOG PS, Eastern Cooperative Oncology Group Performance Status; HR, hazard ratio; ICANS, immune effector cell-associated neurotoxicity syndrome; MM, multiple myeloma; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; R/R, relapsed/refractory; RRMM, relapsed/refractory multiple myeloma; TRM, treatment-related mortality.
References
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