ABSTRACT
Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.5 and 6.0 months, respectively. Safety outcomes between cohorts were comparable. The prior BCMA-TT cohort had a lower overall response rate (74% versus 88%; p = 0.021), median duration of response (7.4 versus 9.6 months; p = 0.03), and median progression-free survival (3.2 months versus 9.0 months; p = 0.0002) compared to the cohort without prior BCMA-TT. All five patients who received a prior anti-BCMA CAR T responded to ide-cel, and survival outcomes were best for this subgroup. In conclusion, treatment with ide-cel yielded meaningful clinical responses in real-world patients exposed to a prior BCMA-TT, though response rates and durability were suboptimal compared to those not treated with a prior BCMA-TT.
Subject(s)
B-Cell Maturation Antigen , Immunotherapy, Adoptive , Multiple Myeloma , Receptors, Chimeric Antigen , Humans , Multiple Myeloma/therapy , B-Cell Maturation Antigen/antagonists & inhibitors , Immunotherapy, Adoptive/methods , Receptors, Chimeric Antigen/therapeutic use , Male , Female , Adult , Middle Aged , Aged , Treatment OutcomeABSTRACT
ABSTRACT: Antibody-drug conjugates (ADCs) have emerged as a treatment option for patients with relapsed/refractory multiple myeloma with the regulatory approval of the first-in-class B-cell maturation antigen (BCMA) ADC belantamab mafodotin. Other BCMA and non-BCMA ADCs are currently in clinical development. Whereas ADCs allow antigen-specific delivery of a chemomoiety to myeloma cells, on-target and off-target effects related to antigen target, antibody, linker, and chemomoiety can also limit these approaches. We review the clinical development of belantamab mafodotin and ongoing efforts to enhance its efficacy while mitigating ocular toxicity. The landscape of other ADCs being evaluated clinically in patients with multiple myeloma will also be reviewed.
