Department of Hematology and Oncology, Nagoya City University Institute of Medical and Pharmaceutical Sciences, Nagoya, Japan.
Department of Hematology, National Hospital Organization Okayama Medical Center, Okayama, Japan.
Int J Hematol. 2023 Nov;118(5):596-608. doi: 10.1007/s12185-023-03652-5. Epub 2023 Sep 5.
Belantamab mafodotin, a B-cell maturation antigen-targeting antibody-drug conjugate (ADC), was investigated in Japanese patients with relapsed/refractory multiple myeloma in Part 1 of the phase I DREAMM-11 study. Patients who had received ≥ 2 prior lines of therapy including a proteasome inhibitor and immunomodulatory agent were eligible. Eight patients received belantamab mafodotin monotherapy at 2.5 mg/kg (n = 4) or 3.4 mg/kg (n = 4) by intravenous infusion every 3 weeks on day 1 of each cycle until disease progression or unacceptable toxicity. Primary objectives were tolerability and safety, and secondary objectives included pharmacokinetics (PK) and efficacy. The most common Grade ≥ 3 adverse event was thrombocytopenia/platelet count decreased (2.5 mg/kg cohort, 100% [4/4]; 3.4 mg/kg cohort, 75% [3/4]), and no dose-limiting toxicities were observed. Ocular events, including keratopathy findings, were observed in most patients (2.5 mg/kg cohort, 100% [4/4]; 3.4 mg/kg cohort, 75% [3/4]) and were managed with dose modifications. All resolved within the study period. Overall response rates were 50% (2/4) in the 2.5 mg/kg cohort and 25% (1/4) in the 3.4 mg/kg cohort. Although PK profiles in Japanese patients varied, individual exposures overlapped with previous results in Western populations. Belantamab mafodotin monotherapy was generally well-tolerated and demonstrated clinical activity at both doses.
贝兰他单抗马妥昔单抗是一种靶向 B 细胞成熟抗原的抗体药物偶联物(ADC),在 DREAMM-11 研究的第 1 部分中被评估用于日本复发/难治性多发性骨髓瘤患者。接受过包括蛋白酶体抑制剂和免疫调节剂在内的至少 2 种既往治疗线的患者有资格入组。8 名患者接受贝兰他单抗马妥昔单抗单药治疗,剂量分别为 2.5mg/kg(n=4)或 3.4mg/kg(n=4),静脉输注,每 3 周一次,每个周期的第 1 天给药,直至疾病进展或出现不可接受的毒性。主要研究终点为耐受性和安全性,次要终点包括药代动力学(PK)和疗效。最常见的≥3 级不良事件是血小板减少症/血小板计数减少(2.5mg/kg 队列,100%[4/4];3.4mg/kg 队列,75%[3/4]),未观察到剂量限制性毒性。大多数患者发生了眼部事件,包括角膜病变(2.5mg/kg 队列,100%[4/4];3.4mg/kg 队列,75%[3/4]),并进行了剂量调整。所有事件均在研究期间内得到解决。2.5mg/kg 队列的总缓解率为 50%(2/4),3.4mg/kg 队列为 25%(1/4)。尽管日本患者的 PK 特征存在差异,但个体暴露与西方人群的既往结果重叠。贝兰他单抗马妥昔单抗单药治疗总体耐受性良好,两个剂量均显示出临床活性。