Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Department of Hematology, Clinica São Germano, São Paulo, Brazil.
Lancet Haematol. 2023 Oct;10(10):e801-e812. doi: 10.1016/S2352-3026(23)00243-0.
Multiple myeloma remains incurable, and heavily pretreated patients with relapsed or refractory disease have few good treatment options. Belantamab mafodotin showed promising results in a phase 2 study of patients with relapsed or refractory multiple myeloma at second or later relapse and a manageable adverse event profile. We aimed to assess the safety and efficacy of belantamab mafodotin in a phase 3 setting.
In the DREAMM-3 open-label phase 3 study, conducted at 108 sites across 18 countries, adult patients were enrolled who had confirmed multiple myeloma (International Myeloma Working Group criteria), ECOG performance status of 0-2, had received two or more previous lines of therapy, including two or more consecutive cycles of both lenalidomide and a proteasome inhibitor, and progressed on, or within, 60 days of completion of the previous treatment. Participants were randomly allocated using a central interactive response technology system (2:1) to receive belantamab mafodotin 2·5 mg/kg intravenously every 21 days, or oral pomalidomide 4·0 mg daily (days 1-21) and dexamethasone 40·0 mg (20·0 mg if >75 years) weekly in a 28-day cycle. Randomisation was stratified by previous anti-CD38 therapy, International Staging System stage, and number of previous therapies. The primary endpoint was progression-free survival in all patients who were randomly allocated. The safety population included all randomly allocated patients who received one or more doses of study treatment. This trial is registered with ClinicalTrials.gov, NCT04162210, and is ongoing. Data cutoff for this analysis was Sept 12, 2022.
Patients were recruited between April 2, 2020, and April 18, 2022. As of September, 2022, 325 patients were randomly allocated (218 to the belantamab mafodotin group and 107 to the pomalidomide-dexamethasone group); 184 (57%) of 325 were male and 141 (43%) of 325 were female, 246 (78%) of 316 were White. Median age was 68 years (IQR 60-74). Median follow-up was 11·5 months (5·5-17·6) for belantamab mafodotin and 10·8 months (5·6-17·1) for pomalidomide-dexamethasone. Median progression-free survival was 11·2 months (95% CI 6·4-14·5) for belantamab mafodotin and 7·0 months (4·6-10·6) for pomalidomide-dexamethasone (hazard ratio 1·03 [0·72-1·47]; p=0·56). Most common grade 3-4 adverse events were thrombocytopenia (49 [23%] of 217) and anaemia (35 [16%]) for belantamab mafodotin, and neutropenia (34 [33%] of 102) and anaemia (18[18%]) for pomalidomide-dexamethasone. Serious adverse events occurred in 94 (43%) of 217 and 40 (39%) of 102 patients, respectively. There were no treatment-related deaths in the belantamab mafodotin group and one (1%) in the pomalidomide-dexamethasone group due to sepsis.
Belantamab mafodotin was not associated with statistically improved progression-free survival compared with standard-of-care, but there were no new safety signals associated with its use. Belantamab mafodotin is being tested in combination regimens for relapsed or refractory multiple myeloma.
GSK (study number 207495).
多发性骨髓瘤仍然无法治愈，且复发或难治的大量经治患者治疗选择有限。在复发或难治多发性骨髓瘤患者中开展的 2 期研究显示，贝兰他单抗mafodotin 疗效良好，这些患者为第 2 次或更晚复发且复发后接受过两种或以上治疗（包括两种或以上连续周期的来那度胺和蛋白酶体抑制剂）、治疗后或末次治疗结束后 60 天内进展的患者，该药物具有可管理的不良事件特征。本研究旨在评估贝兰他单抗 mafodotin 在 3 期研究背景下的安全性和疗效。
在 18 个国家的 108 个地点开展的、开放性标签、3 期 DREAMM-3 研究中，入组了经确认患有多发性骨髓瘤（国际骨髓瘤工作组标准）、ECOG 体能状态为 0-2、接受过两种或以上治疗（包括两种或以上连续周期的来那度胺和蛋白酶体抑制剂）且治疗后或末次治疗结束后 60 天内进展的成年患者。采用中央交互式反应技术系统（2:1）将患者随机分配，接受贝兰他单抗 mafodotin 2·5 mg/kg 每 21 天静脉输注，或接受口服泊马度胺 4·0 mg/天（第 1-21 天）和每周口服地塞米松 40·0 mg（＞75 岁患者为 20·0 mg），28 天为 1 个治疗周期。随机分组根据既往抗 CD38 治疗、国际分期系统（ISS）分期和既往治疗次数进行分层。主要终点为所有随机分配患者的无进展生存期。安全性人群包括接受过 1 次或以上研究治疗的所有随机分配患者。本试验在 ClinicalTrials.gov 注册，编号为 NCT04162210，正在进行中。本次分析的数据截止日期为 2022 年 9 月 12 日。
患者于 2020 年 4 月 2 日至 2022 年 4 月 18 日入组。截至 2022 年 9 月，325 例患者被随机分配（贝兰他单抗 mafodotin 组 218 例，泊马度胺-地塞米松组 107 例）；325 例患者中，184 例（57%）为男性，141 例（43%）为女性，316 例（97%）为白人，中位年龄为 68 岁（IQR 60-74）。中位随访时间为贝兰他单抗 mafodotin 组 11·5 个月（5·5-17·6），泊马度胺-地塞米松组 10·8 个月（5·6-17·1）。贝兰他单抗 mafodotin 组的中位无进展生存期为 11·2 个月（95%CI 6·4-14·5），泊马度胺-地塞米松组为 7·0 个月（4·6-10·6）（风险比 1·03 [0·72-1·47]；p=0·56）。最常见的 3-4 级不良事件为贝兰他单抗 mafodotin 组的血小板减少（217 例患者中有 49 例[23%]）和贫血（35 例[16%]），泊马度胺-地塞米松组为中性粒细胞减少（102 例患者中有 34 例[33%]）和贫血（18 例[18%]）。分别有 94 例（43%）和 40 例（39%）患者发生严重不良事件。贝兰他单抗 mafodotin 组无治疗相关死亡，泊马度胺-地塞米松组有 1 例（1%）因脓毒症死亡。
与标准护理相比，贝兰他单抗 mafodotin 并未显著改善无进展生存期，但使用该药未出现新的安全性信号。贝兰他单抗 mafodotin 正在复发或难治性多发性骨髓瘤的联合治疗方案中进行测试。
GSK（研究编号 207495）。
