University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Blood Cancer J. 2024 Apr 22;14(1):69. doi: 10.1038/s41408-024-01030-w.
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) 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). Video Abstract.
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）患者中显示出有前景的疗效。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。在这里，我们对伴有高危细胞遗传学异常（HRCAs；del[17p]、t[4;14]、t[14;16]、t[14;20]或 gain/amp[1q21]）的患者进行了一项事后分析。在 123 例接受 D-KRd 治疗的患者中，43.1%、37.4%和 19.5%的患者 HRCAs 为 0、1 或≥2。在 120 例接受 D-RVd 治疗的患者中，55.8%、28.3%和 10.8%的患者 HRCAs 为 0、1 或≥2。D-KRd 治疗 0、1 或≥2 HRCAs 的完全缓解或更好（研究最佳）率分别为 90.6%、89.1%和 70.8%，D-RVd 治疗的相应比率分别为 90.9%、78.8%和 61.5%。在中位随访（MASTER 为 31.1 个月；GRIFFIN 为随机分组患者的 49.6 个月和安全性导入期患者的 59.5 个月）时，通过下一代测序（10）评估的 MRD 阴性率为 D-KRd 治疗的 0、1 或≥2 HRCAs 分别为 80.0%、86.4%和 83.3%，D-RVd 治疗的相应比率分别为 76.1%、55.9%和 61.5%。无进展生存期（PFS）在两项研究中相似，0 或 1 个 HRCAs 优于≥2 个 HRCAs：D-KRd 治疗的 36 个月 PFS 率分别为 89.9%、86.2%和 52.4%，D-RVd 治疗的相应比率分别为 96.7%、90.5%和 53.5%。这些数据支持使用含达雷妥尤单抗的方案治疗伴有 HRCAs 的适合移植的 NDMM；然而，对于超高危疾病（≥2 HRCAs），还需要其他策略。视频摘要。
