Debulking Chemotherapy Can Overcome Primary Resistance to Teclistamab in Relapsed/Refractory Multiple Myeloma

作者：Rintu Sharma, Andrée-Anne Pelland, Katherine Lajkosz, Esther Masih-Khan, Harjot Vohra, Sita Bhella, Christine I. Chen, Vishal Kukreti, A. Keith Stewart, Suzanne Trudel, Chloe Yang, Donna E. Reece, Chris Venner, Guido Lancman · 发表于：Blood Cancer Discovery · 年份：2026 · DOI：10.1158/2643-3230.bcd-25-0372 · 被引用次数：1 · 研究领域：Multiple Myeloma Research and Treatments、Malaria Research and Control、Cancer Treatment and Pharmacology

Bispecific antibodies have revolutionized the treatment of multiple myeloma; however, primary treatment failure occurs in 30% to 40% of patients. In this study, we analyzed correlates of response to teclistamab and strategies to overcome primary resistance. Across two independent cohorts (n = 90), we developed the high risk of primary resistance (Hi-MM) variable, defined by extramedullary disease, plasma cell leukemia, bone marrow plasmacytosis ≥50%, or transfusion within 30 days, as a composite correlate of nonresponse. Patients without Hi-MM had overall response rates of 84% to 96% (vs. 20%-40% with Hi-MM) and significantly superior progression-free survival (P < 0.001) and overall survival (P < 0.001). Debulking chemotherapy was utilized in 19 patients; 79% then responded to teclistamab, including 100% who no longer had Hi-MM. All four patients who were primary refractory to a BCMA bispecific immediately prior to debulking then achieved deep responses to teclistamab. In conclusion, simple clinical parameters correlate with response to teclistamab, whereas debulking chemotherapy can overcome Hi-MM and successfully bridge patients to teclistamab or salvage nonresponders. SIGNIFICANCE: A clinically assessable composite variable, Hi-MM, identifies patients who may benefit from debulking chemotherapy prior to teclistamab. By treating patients at a time of low disease burden or using debulking chemotherapy for those with a high risk of resistance, nearly all patients can benefit...