Emerging therapeutic agents in multiple myeloma: highlights from the 2024 ASH annual meeting

Abstract

Novel agents with innovative mechanisms of action were updated at the latest 2024 ASH Annual Meeting, some featuring first trials in combinations. Advances span new antibodies, bispecific T-cell engagers, next-generation CELMoDs, and agents targeting previously unexplored pathways in relapsed/refractory multiple myeloma. Key updates include: Cevostamab (FcRH5×CD3) demonstrated a 30.2% overall response rate in patients who underwent BCMA-targeted treatment and 60.6% in BCMA-targeted naïve patients;the triple-step dosing strategy reduced cytokine release syndrome. Lisaftoclax (APG-2575, BCL-2 inhibitor) displayed overall response rates ranging from 61.3 to 100% and ≥ VGPR rates of 32.3-100%, supporting enhanced response depth with favorable safety in combination regimens. Inobrodib (CCS1477, p300/CBP inhibitor) plus lenalidomide achieved a 71% overall response rate in pomalidomide-refractory patients, marking the first oral epigenetic modulator to reverse immunomodulatory drug resistance. Elranatamab (ELRA, BCMA×CD3) combined with carfilzomib and dexamethasone yielded an 83.3% overall response rate with a median duration of response not reached. Mezigdomide (MEZI, CELMoD) showed an 85.7% overall response rate and 17.5-month progression-free survival in Lenalidomide-refractory patients. ISB 2001 (BCMA×CD38×CD3 tri-specific antibody): achieved a 90% overall response rate at ≥ 50 µg/kg in heavily pretreated patients, with low-grade cytokine release syndrome observed. Through multi-targeted design, reversal of drug resistance mechanisms, and optimized combination strategies, treatment approaches for relapsed/refractory multiple myeloma are evolving toward greater precision, durability, and individualization.

Keywords: CELMoD; Cevostamab; Elranatamab; ISB 2001; Inobrodib; Lisaftoclax; Mezigdomide; Multiple myeloma; Tri-specific antibody.