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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-03050-2

摘要内容如下：

CD38靶向免疫疗法被批准与来那度胺和地塞米松联合用于不适合移植（Ti）的新诊断多发性骨髓瘤（NDMM）患者，并被认为是最佳治疗标准（SOC）。为了改善目前的SOC，我们评估了每周硼替佐米（V）对伊沙昔单抗联合来那度胺和地塞米松的附加价值（Isard与ISA-VRD）。这项法语组间骨髓瘤3期研究将270名年龄在65-79岁的NDMM患者随机分为ISARD组和ISA-VRD组。主要终点是在随机分组后18个月时，下一代测序的微小残留病（MRD）阴性率为10-5。关键次要终点包括缓解率、MRD评估率、生存率和安全性。Isard中有35名患者（26%，95%可信区间（CI）19-34）报告了18个月10-5时的MRD阴性率，而ISA-VRD中有71名患者（53%，95%CI 44-61）报告了18个月10-5时的MRD阴性率（MRD阴性的比值比为3.16，95%CI 1.89-5.28，P<0.0001）。在10-5和10-6时，各亚组的MRD获益是一致的，并且在第12个月时已经观察到。在18个月时，ISA-VRD的完全缓解或更好的患者比例更高（58%对33%；P<0.0001），MRD阴性和完全缓解或更好的比例也是如此（37%对17%；P=0.0003）。中位随访时间为23.5个月，未观察到生存时间差异（未成熟数据）。每周加用硼替佐米不会显著影响Isard的相对剂量强度。与Isard相比，ISA-VRD显著增加了MRD终点，包括主要终点10-5的18个月阴性率。本研究建议将ISA-VRD作为Ti的NDMM患者的新SOC。ClinicalTrials.gov标识符：NCT04751877。

英文原文如下：

Abstracts

CD38-targeting immunotherapy is approved in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM) that are transplant ineligible (TI) and is considered the best standard of care (SOC). To improve current SOC, we evaluated the added value of weekly bortezomib (V) to isatuximab plus lenalidomide and dexamethasone (IsaRd versus Isa-VRd). This Intergroupe Francophone of Myeloma phase 3 study randomized 270 patients with NDMM that were TI, aged 65-79 years, to IsaRd versus Isa-VRd arms. The primary endpoint was a minimal residual disease (MRD) negativity rate at 10-5 by next-generation sequencing at 18 months from randomization. Key secondary endpoints included response rates, MRD assessment rates, survival and safety. The 18-month MRD negativity rates at 10-5 were reported in 35 patients (26%, 95% confidence interval (CI) 19-34) in IsaRd versus 71 (53%, 95% CI 44-61) in Isa-VRd (odds ratio for MRD negativity 3.16, 95% CI 1.89-5.28, P < 0.0001). The MRD benefit was consistent across subgroups at 10-5 and 10-6, and was already observed at month 12. The proportion of patients with complete response or better at 18 months was higher with Isa-VRd (58% versus 33%; P < 0.0001), as was the proportion of MRD negativity and complete response or better (37% versus 17%; P = 0.0003). At a median follow-up of 23.5 months, no difference was observed for survival times (immature data). The addition of weekly bortezomib did not significantly affect the relative dose intensity of IsaRd. Isa-VRd significantly increased MRD endpoints, including the 18-month negativity rate at 10-5, the primary endpoint, compared with IsaRd. This study proposes Isa-VRd as a new SOC for patients with NDMM that are TI. ClinicalTrials.gov identifier: NCT04751877 .

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