Indiana University Simon Cancer Center and Roudebush VAMC, Indianapolis, Indiana, USA.
Arnie Charbonneau Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.
Cancer. 2024 Aug 1;130(15):2629-2641. doi: 10.1002/cncr.35319. Epub 2024 Apr 17.
Belantamab mafodotin (belamaf) has shown promising antimyeloma activity in relapsed or refractory multiple myeloma (RRMM) as a single agent. It was hypothesized that its multimodal activity may be enhanced by programmed cell death protein 1 pathway inhibition and activation of T cell-mediated antitumor responses. This study investigated the efficacy and safety of belamaf with pembrolizumab in patients with RRMM.
DREAMM-4 (NCT03848845) was an open-label, single-arm, phase 1/2 study divided into dose-escalation (part 1) and dose-expansion (part 2) phases. Patients were ≥18 years old with ≥3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 agent. Patients received belamaf (2.5 or 3.4 mg/kg, part 1; 2.5 mg/kg, part 2) and 200 mg pembrolizumab for ≤35 cycles.
Of 41 enrolled patients, 34 (n = 6 part 1, n = 28 part 2) who received 2.5 mg/kg belamaf plus pembrolizumab were included in this final analysis. Sixteen patients (47%) achieved an overall response. Minimal residual disease negativity was achieved in three of 10 patients who had very good partial response or better. Five of eight patients who had prior anti-B-cell maturation antigen therapy achieved partial response or better, including two who had B-cell maturation antigen-refractory disease. Common grade ≥3 adverse events were keratopathy (38%) and thrombocytopenia (29%). Despite belamaf-related ocular events, quality-of-life measures remained stable over time. No new safety signals were observed.
The results of DREAMM-4 demonstrated clinical activity and a favorable safety profile of belamaf plus pembrolizumab in patients with RRMM. This trial is registered at www.
gov as NCT03848845.
贝兰他单抗（belamaf）作为单一药物在复发/难治性多发性骨髓瘤（RRMM）中显示出有前景的抗骨髓瘤活性。据推测，其多模式活性可能通过程序性细胞死亡蛋白 1 途径抑制和激活 T 细胞介导的抗肿瘤反应得到增强。本研究调查了 belamaf 联合 pembrolizumab 在 RRMM 患者中的疗效和安全性。
DREAMM-4（NCT03848845）是一项开放标签、单臂、1/2 期研究，分为剂量递增（第 1 部分）和剂量扩展（第 2 部分）阶段。患者年龄≥18 岁，接受过≥3 线治疗，包括蛋白酶体抑制剂、免疫调节剂和抗 CD38 药物。患者接受 belamaf（2.5 或 3.4 mg/kg，第 1 部分；2.5 mg/kg，第 2 部分）和 200 mg pembrolizumab，最多 35 个周期。
在 41 名入组患者中，有 34 名（n=6 名第 1 部分，n=28 名第 2 部分）接受 2.5 mg/kg belamaf 联合 pembrolizumab的患者纳入本最终分析。16 名患者（47%）达到总体缓解。在 10 名获得非常好的部分缓解或更好的患者中，有 3 名达到微小残留病灶阴性。8 名有既往抗 B 细胞成熟抗原治疗的患者中有 5 名获得部分缓解或更好，包括 2 名 B 细胞成熟抗原难治性疾病患者。常见的≥3 级不良事件是角膜炎（38%）和血小板减少症（29%）。尽管有 belamaf 相关的眼部事件，但随着时间的推移，生活质量指标保持稳定。未观察到新的安全性信号。
DREAMM-4 的结果表明，在 RRMM 患者中，belamaf 联合 pembrolizumab 具有临床活性和良好的安全性。该试验在 www.clinicaltrials.gov 注册，编号为 NCT03848845。
