文章：

达雷妥尤单抗四联疗法治疗新诊断的细胞遗传学高危适合移植的多发性骨髓瘤

Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk

原文发布日期：2024-04-22

DOI: 10.1038/s41408-024-01030-w

类型: Article

开放获取: 是

英文摘要：

In the MASTER study (NCT03224507), daratumumab+carfilzomib/lenalidomide/dexamethasone (D-KRd) demonstrated promising efficacy in transplant-eligible newly diagnosed multiple myeloma (NDMM). In GRIFFIN (NCT02874742), daratumumab+lenalidomide/bortezomib/dexamethasone (D-RVd) improved outcomes for transplant-eligible NDMM. Here, we present a post hoc analysis of patients with high-risk cytogenetic abnormalities (HRCAs; del[17p], t[4;14], t[14;16], t[14;20], or gain/amp[1q21]). Among 123 D-KRd patients, 43.1%, 37.4%, and 19.5% had 0, 1, or ≥2 HRCAs. Among 120 D-RVd patients, 55.8%, 28.3%, and 10.8% had 0, 1, or ≥2 HRCAs. Rates of complete response or better (best on study) for 0, 1, or ≥2 HRCAs were 90.6%, 89.1%, and 70.8% for D-KRd, and 90.9%, 78.8%, and 61.5% for D-RVd. At median follow-up (MASTER, 31.1 months; GRIFFIN, 49.6 months for randomized patients/59.5 months for safety run-in patients), MRD-negativity rates as assessed by next-generation sequencing (10–5) were 80.0%, 86.4%, and 83.3% for 0, 1, or ≥2 HRCAs for D-KRd, and 76.1%, 55.9%, and 61.5% for D-RVd. PFS was similar between studies and superior for 0 or 1 versus ≥2 HRCAs: 36-month PFS rates for D-KRd were 89.9%, 86.2%, and 52.4%, and 96.7%, 90.5%, and 53.5% for D-RVd. These data support the use of daratumumab-containing regimens for transplant-eligible NDMM with HCRAs; however, additional strategies are needed for ultra-high–risk disease (≥2 HRCAs).
 

摘要翻译： 

在MASTER研究（NCT03224507）中，达雷妥尤单抗+卡非佐米/来那度胺/地塞米松（D-KRd）在适合移植的新诊断多发性骨髓瘤（NDMM）患者中显示出良好的疗效。在GRIFFIN研究（NCT02874742）中，达雷妥尤单抗+来那度胺/硼替佐米/地塞米松（D-RVd）改善了适合移植的NDMM患者的结局。本文对具有高危细胞遗传学异常（HRCAs；包括del[17p]、t[4;14]、t[14;16]、t[14;20]或gain/amp[1q21]）的患者进行了事后分析。在123例D-KRd患者中，43.1%、37.4%和19.5%分别具有0、1或≥2种HRCAs。在120例D-RVd患者中，55.8%、28.3%和10.8%分别具有0、1或≥2种HRCAs。在D-KRd组中，0、1或≥2种HRCAs患者的完全缓解或更佳缓解率（研究期间最佳）分别为90.6%、89.1%和70.8%；在D-RVd组中，分别为90.9%、78.8%和61.5%。在中位随访时间（MASTER研究31.1个月；GRIFFIN研究中随机分组患者49.6个月/安全性导入期患者59.5个月）下，通过新一代测序（10–5）评估的MRD阴性率在D-KRd组0、1或≥2种HRCAs患者中分别为80.0%、86.4%和83.3%，在D-RVd组中分别为76.1%、55.9%和61.5%。两项研究中的无进展生存期（PFS）相似，且0或1种HRCAs患者优于≥2种HRCA患者：D-KRd组的36个月PFS率分别为89.9%、86.2%和52.4%，D-RVd组分别为96.7%、90.5%和53.5%。这些数据支持对伴有HRCAs的适合移植NDMM患者使用含达雷妥尤单抗的方案；然而，针对超高危疾病（≥2种HRCAs）仍需额外治疗策略。

原文链接：

Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk