From the Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens (M.A.D.), and General Hospital Evangelismos (S.D.) - both in Athens; the Department of Hematology, Ankara Liv Hospital, Istinye University, Ankara, Turkey (M.B.); the Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno (L.P.), the First Faculty of Medicine, Charles University, and General Hospital, Prague (I.S.), and the Fourth Department of Internal Medicine-Hematology, University Hospital Hradec Králové, and Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové (J.R.) - all in the Czech Republic; Leningrad Regional Clinical Hospital, Saint Petersburg, Russia (V.V.); the University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia (H.Q.); Medical University of Lodz, Łódź, Poland (P.R.); Sungkyunkwan University and Samsung Medical Center, Seoul, South Korea (K.K.); IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, and Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy (M.C.); the Division of Clinical Oncology-Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo (K.S.); GSK, Durham, NC (K.M.); GSK, Philadelphia (F.P.), and GSK, Collegeville (N.S., B.E.K., J.O.) - both in Pennsylvania; GSK, Stevenage, United Kingdom (A.P.-J.); GSK, Waltham, MA (X.L.Z., G.F.); the Hematology Department, Cancer Research Center-Instituto de Investigación Biomédica de Salamanca, University Hospital of Salamanca, Salamanca, Spain (M.-V.M.); and the Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto (S.T.).
N Engl J Med. 2024 Aug 1;391(5):408-421. doi: 10.1056/NEJMoa2403407. Epub 2024 Jun 2.
Triplet or quadruplet therapies incorporating proteasome inhibitors, immunomodulators, and anti-CD38 antibodies have led to prolonged survival among patients with newly diagnosed multiple myeloma; however, most patients have a relapse. Frontline lenalidomide therapy has increased the number of patients with lenalidomide-refractory disease at the time of the first relapse.
In this phase 3, randomized, open-label trial, we evaluated belantamab mafodotin, pomalidomide, and dexamethasone (BPd), as compared with pomalidomide, bortezomib, and dexamethasone (PVd), in lenalidomide-exposed patients who had relapsed or refractory myeloma after at least one line of therapy. The primary end point was progression-free survival. Disease response and safety were also assessed.
A total of 302 patients underwent randomization; 155 were assigned to the BPd group, and 147 to the PVd group. At a median follow-up of 21.8 months (range, <0.1 to 39.2), the 12-month estimated progression-free survival with BPd was 71% (95% confidence interval [CI], 63 to 78), as compared with 51% (95% CI, 42 to 60) with PVd (hazard ratio for disease progression or death, 0.52; 95% CI, 0.37 to 0.73; P<0.001). Data on overall survival were immature. The percentage of patients with a response to treatment (partial response or better) was 77% (95% CI, 70 to 84) in the BPd group and 72% (95% CI, 64 to 79) in the PVd group; 40% (95% CI, 32 to 48) and 16% (95% CI, 11 to 23), respectively, had a complete response or better. Grade 3 or higher adverse events occurred in 94% of the patients in the BPd group and 76% of those in the PVd group. Ocular events occurred in 89% of the patients who received BPd (grade 3 or 4 in 43%) and 30% of those who received PVd (grade 3 or 4 in 2%); ocular events in the BPd group were managed with belantamab mafodotin dose modification. Ocular events led to treatment discontinuation in 9% of the patients in the BPd group and in no patients in the PVd group.
Among lenalidomide-exposed patients with relapsed or refractory myeloma, BPd conferred a significantly greater benefit than PVd with respect to progression-free survival, as well as deeper, more durable responses. Ocular events were common but were controllable by belantamab mafodotin dose modification. (Funded by GSK; DREAMM-8 ClinicalTrials.gov number, NCT04484623; EudraCT number, 2018-004354-21.).
包含蛋白酶体抑制剂、免疫调节剂和抗 CD38 抗体的三联或四联疗法已使新诊断多发性骨髓瘤患者的生存期延长；然而，大多数患者会复发。一线来那度胺治疗增加了首次复发时来那度胺耐药疾病患者的数量。
在这项 3 期、随机、开放标签试验中，我们评估了 belantamab mafodotin、泊马度胺和地塞米松（BPd）与泊马度胺、硼替佐米和地塞米松（PVd）相比，在至少接受过一线治疗后复发或难治性骨髓瘤的来那度胺暴露患者中的疗效。主要终点是无进展生存期。还评估了疾病反应和安全性。
共有 302 名患者接受了随机分组；155 名患者被分配至 BPd 组，147 名患者被分配至 PVd 组。在中位随访 21.8 个月（范围，<0.1 至 39.2）时，BPd 的 12 个月估计无进展生存率为 71%（95%CI，63 至 78），而 PVd 组为 51%（95%CI，42 至 60）（疾病进展或死亡的风险比，0.52；95%CI，0.37 至 0.73；P<0.001）。总生存数据不成熟。BPd 组有 77%（95%CI，70 至 84）的患者对治疗有反应（部分缓解或更好），PVd 组有 72%（95%CI，64 至 79）；分别有 40%（95%CI，32 至 48）和 16%（95%CI，11 至 23）患者有完全缓解或更好。BPd 组 94%的患者和 PVd 组 76%的患者发生了 3 级或更高的不良事件。BPd 组 89%的患者发生眼部事件（43%为 3 级或 4 级），而 PVd 组为 30%（2 级或 3 级为 4 级）；BPd 组的眼部事件通过调整 belantamab mafodotin 剂量得到控制。BPd 组有 9%的患者因眼部事件而停止治疗，而 PVd 组无患者因眼部事件而停止治疗。
在来那度胺暴露的复发或难治性骨髓瘤患者中，BPd 与 PVd 相比，在无进展生存期方面具有显著更大的益处，并且具有更深、更持久的反应。眼部事件很常见，但通过调整 belantamab mafodotin 剂量可以控制。（由 GSK 资助；DREAMM-8 临床试验.gov 编号，NCT04484623；EudraCT 编号，2018-004354-21）。
