Levine Cancer Institute, Atrium Health, Charlotte, NC.
Department of Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC.
Blood Adv. 2021 Feb 23;5(4):1092-1096. doi: 10.1182/bloodadvances.2020003642.
The phase 2 GRIFFIN study of daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) for transplant-eligible, newly diagnosed multiple myeloma included a safety run-in phase followed by a randomized phase. The ongoing randomized phase has met its prespecified primary end point of an improved stringent complete response (sCR) rate after consolidation for D-RVd (reported elsewhere). Final analysis of the safety run-in cohort is reported herein and provides longer follow-up (median, 40.8 months) encompassing daratumumab plus lenalidomide (D-R) maintenance therapy. Patients in the safety run-in cohort (N = 16) received 4 induction cycles (D-RVd), high-dose melphalan supported by autologous stem cell transplant, 2 consolidation cycles (D-RVd), and 24 months of maintenance (D-R). By the end of consolidation, all patients had responded, with a best response of sCR in 9 (56.3%) patients; 8 (50.0%) patients were minimal residual disease (MRD) negative (10‒5 threshold). After maintenance, 15 (93.8%) patients had achieved a best response of sCR, and 13 (81.3%) patients were MRD (10‒5) negative. Estimated 36-month progression-free and overall survival rates were 78.1% and 93.8%, respectively. One death from progressive disease occurred in the patient who did not achieve sCR. Observed safety profiles were consistent with daratumumab and RVd. With >3 years of median follow-up, D-RVd achieved durable responses that deepened with D-R maintenance. This study was registered at www.clinicaltrials.gov as #NCT02874742.
GRIFFIN 研究是一项评估达雷妥尤单抗联合来那度胺/硼替佐米/地塞米松（D-RVd）方案用于适合移植的初诊多发性骨髓瘤患者的疗效和安全性的Ⅱ期临床研究。该研究包括一个安全性爬坡阶段和一个随机阶段。目前正在进行的随机阶段已经达到了其预设的主要终点，即 D-RVd 巩固治疗后的严格完全缓解（sCR）率提高（详见其他报道）。本文报告了安全性爬坡队列的最终分析结果，提供了更长时间的随访（中位随访时间 40.8 个月），包括达雷妥尤单抗联合来那度胺（D-R）维持治疗。安全性爬坡队列（n=16）患者接受了 4 个诱导周期（D-RVd）、大剂量马法兰联合自体造血干细胞移植、2 个巩固周期（D-RVd）和 24 个月的维持治疗（D-R）。在巩固治疗结束时，所有患者均有缓解，9 例（56.3%）患者达到 sCR 最佳缓解，8 例（50.0%）患者达到微小残留病灶（MRD）阴性（10‒5 界值）。维持治疗后，15 例（93.8%）患者达到 sCR 最佳缓解，13 例（81.3%）患者达到 MRD（10‒5）阴性。估计 36 个月无进展生存率和总生存率分别为 78.1%和 93.8%。1 例未达到 sCR 的患者死于疾病进展。观察到的安全性特征与达雷妥尤单抗和 RVd 一致。在中位随访时间超过 3 年后，D-RVd 实现了持久缓解，并且在 D-R 维持治疗后缓解程度加深。本研究在 www.clinicaltrials.gov 注册，编号为 #NCT02874742。
