文章：

达雷妥尤单抗治疗适合移植的新诊断多发性骨髓瘤患者：GRIFFIN研究中临床相关亚组的最终分析

Daratumumab in transplant-eligible patients with newly diagnosed multiple myeloma: final analysis of clinically relevant subgroups in GRIFFIN

原文发布日期：2024-07-08

DOI: 10.1038/s41408-024-01088-6

类型: Article

开放获取: 是

英文摘要：

The randomized, phase 2 GRIFFIN study (NCT02874742) evaluated daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM). We present final post hoc analyses (median follow-up, 49.6 months) of clinically relevant subgroups, including patients with high-risk cytogenetic abnormalities (HRCAs) per revised definition (del[17p], t[4;14], t[14;16], t[14;20], and/or gain/amp[1q21]). Patients received 4 induction cycles (D-RVd/RVd), high-dose therapy/transplant, 2 consolidation cycles (D-RVd/RVd), and lenalidomide±daratumumab maintenance (≤ 2 years). Minimal residual disease–negativity (10−5) rates were higher for D-RVd versus RVd in patients ≥ 65 years (67.9% vs 17.9%), with HRCAs (54.8% vs 32.4%), and with gain/amp(1q21) (61.8% vs 28.6%). D-RVd showed a trend toward improved progression-free survival versus RVd (hazard ratio [95% confidence interval]) in patients ≥ 65 years (0.29 [0.06–1.48]), with HRCAs (0.38 [0.14–1.01]), and with gain/amp(1q21) (0.42 [0.14–1.27]). In the functional high-risk subgroup (not MRD negative at the end of consolidation), the hazard ratio was 0.82 (0.35–1.89). Among patients ≥ 65 years, grade 3/4 treatment-emergent adverse event (TEAE) rates were higher for D-RVd versus RVd (88.9% vs 77.8%), as were TEAEs leading to discontinuation of ≥ 1 treatment component (37.0% vs 25.9%). One D-RVd patient died due to an unrelated TEAE. These results support the addition of daratumumab to RVd in transplant-eligible patients with high-risk NDMM.
 

摘要翻译： 

随机II期GRIFFIN研究（NCT02874742）评估了达雷妥尤单抗联合来那度胺/硼替佐米/地塞米松（D-RVd）方案在适合移植的新诊断多发性骨髓瘤（NDMM）患者中的应用。本文呈现临床相关亚组的最终事后分析结果（中位随访时间49.6个月），包括符合修订定义的高危细胞遗传学异常（HRCA）患者（del[17p]、t[4;14]、t[14;16]、t[14;20]和/或gain/amp[1q21]）。患者接受4个诱导周期（D-RVd/RVd）、大剂量治疗/移植、2个巩固周期（D-RVd/RVd）以及来那度胺±达雷妥尤单抗维持治疗（≤2年）。在年龄≥65岁（67.9% vs 17.9%）、伴HRCA（54.8% vs 32.4%）及伴gain/amp(1q21)（61.8% vs 28.6%）的患者中，D-RVd组的微小残留病灶阴性率（10的负5次方）均高于RVd组。在年龄≥65岁（风险比[95%置信区间]：0.29 [0.06–1.48]）、伴HRCA（0.38 [0.14–1.01]）及伴gain/amp(1q21)（0.42 [0.14–1.27]）患者中，D-RVd组较RVd组呈现无进展生存期改善趋势。在功能性高危亚组（巩固治疗结束时未达MRD阴性）中，风险比为0.82（0.35–1.89）。在≥65岁患者中，D-RVd组的3/4级治疗期间不良事件发生率高于RVd组（88.9% vs 77.8%），导致≥1种治疗成分停药的TEAE发生率亦更高（37.0% vs 25.9%）。1例D-RVd组患者因不相关TEAE死亡。这些结果支持在适合移植的高危NDMM患者的RVd方案中加入达雷妥尤单抗。

原文链接：

Daratumumab in transplant-eligible patients with newly diagnosed multiple myeloma: final analysis of clinically relevant subgroups in GRIFFIN