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<p>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&#xa0;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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • Qing Zhang,
  • Yongping Song,
  • Keshu Zhou,
  • Quande Lin

摘要

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.