医学
中性粒细胞减少症
不利影响
内科学
耐火材料(行星科学)
多发性骨髓瘤
发热性中性粒细胞减少症
胃肠病学
临床研究阶段
进行性疾病
外科
临床试验
毒性
化疗
天体生物学
物理
作者
Sarah A. Holstein,Shebli Atrash,Hira Mian,Meletios Α. Dimopoulos,Fredrik Schjesvold,Rakesh Popat,Nishi Shah,Moshe E. Gatt,Christian B. Gocke,Laurent Frenzel,Cyrille Touzeau,Meral Beksaç,Salomon Manier,Hila Magen,Patrick M. Travis,Omar Nadeem,Kaveri Suryanarayan,Cheryl Li,Shuli Li,Allison Nelson
出处
期刊:Blood
[Elsevier BV]
日期:2025-04-25
卷期号:146 (9): 1051-1064
标识
DOI:10.1182/blood.2024027873
摘要
Abstract Modakafusp alfa is a first-in-class immunocytokine-directing interferon alfa to CD38+ cells. Our previous phase 1/2 trial identified 2 potential phase 2 doses of modakafusp alfa for patients with relapsed/refractory multiple myeloma (RRMM): 1.5 or 3 mg/kg every 4 weeks. The overall response rate (ORR) among 30 patients treated at 1.5 mg/kg was 43%. This phase 2 dose optimization study randomized 147 patients with triple-class refractory disease and ≥3 previous lines of therapy 1:1 to modakafusp alfa 120 mg (n = 71) or 240 mg (n = 75) every 4 weeks (fixed-dose equivalents of 1.5 and 3 mg/kg every 4 weeks). Patients had received a median of 6 previous lines of therapy; 66% were penta-exposed and 45% had previously been exposed to anti–B-cell maturation antigen (BCMA) therapy. Modakafusp alfa development was discontinued for strategic reasons by the sponsor and the study was terminated early. At median follow-up of 7.3 and 7.6 months in the 120- and 240-mg arms, ORRs were 32% and 41%, and median progression-free survival was 4.1 and 5.3 months, respectively. ORRs were higher in patients who had not received previous BCMA therapy (46% vs 29%). The most common treatment-related adverse events (TEAEs) in the 120- and 240-mg arms were thrombocytopenia (75% and 84%; grade ≥3, 55% and 61%; respectively) and neutropenia (68% and 73%; grade ≥3, 56% and 68%; respectively); 90% and 96% of patients, respectively, experienced grade ≥3 TEAEs; 39% and 44%, respectively, experienced serious TEAEs. Our results confirm the efficacy of single-agent modakafusp alfa for patients with RRMM. This trial was registered at www.clinicaltrials.gov as #NCT03215030.
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