达雷妥尤单抗、硼替佐米和地塞米松治疗复发或难治性多发性骨髓瘤：基于细胞遗传学风险的 CASTOR 亚组分析。
Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk.
机构信息
Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Malignant Haematology and Stem Cell Transplantation Service, Alfred Health-Monash University, Melbourne, Australia.
出版信息
J Hematol Oncol. 2020 Aug 20;13(1):115. doi: 10.1186/s13045-020-00948-5.
BACKGROUND
Multiple myeloma (MM) patients with high cytogenetic risk have poor outcomes. In CASTOR, daratumumab plus bortezomib/dexamethasone (D-Vd) prolonged progression-free survival (PFS) versus bortezomib/dexamethasone (Vd) alone and exhibited tolerability in patients with relapsed or refractory MM (RRMM).
METHODS
This subgroup analysis evaluated D-Vd versus Vd in CASTOR based on cytogenetic risk, determined using fluorescence in situ hybridization and/or karyotype testing performed locally. High-risk patients had t(4;14), t(14;16), and/or del17p abnormalities. Minimal residual disease (MRD; 10 sensitivity threshold) was assessed via the clonoSEQ® assay V2.0. Of the 498 patients randomized, 40 (16%) in the D-Vd group and 35 (14%) in the Vd group were categorized as high risk.
RESULTS
After a median follow-up of 40.0 months, D-Vd prolonged median PFS versus Vd in patients with standard (16.6 vs 6.6 months; HR, 0.26; 95% CI, 0.19-0.37; P < 0.0001) and high (12.6 vs 6.2 months; HR, 0.41; 95% CI, 0.21-0.83; P = 0.0106) cytogenetic risk. D-Vd achieved deep responses, including higher rates of MRD negativity and sustained MRD negativity versus Vd, regardless of cytogenetic risk. The safety profile was consistent with the overall population of CASTOR.
CONCLUSION
These updated data reinforce the effectiveness and tolerability of daratumumab-based regimens for RRMM, regardless of cytogenetic risk status.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT02136134 . Registered 12 May 2014.
背景
细胞遗传学风险高的多发性骨髓瘤（MM）患者预后较差。在 CASTOR 研究中，与硼替佐米/地塞米松（Vd）相比，达雷妥尤单抗联合硼替佐米/地塞米松（D-Vd）延长了无进展生存期（PFS），并且在复发或难治性 MM（RRMM）患者中具有可耐受性。
方法
本亚组分析根据细胞遗传学风险，采用荧光原位杂交和/或局部染色体核型检测来评估 CASTOR 中 D-Vd 与 Vd 的疗效。高危患者具有 t(4;14)、t(14;16) 和/或 del17p 异常。微小残留疾病（MRD；10 灵敏度阈值）通过 clonoSEQ®V2.0 检测进行评估。在 498 例随机患者中，D-Vd 组中有 40 例（16%），Vd 组中有 35 例（14%）归类为高危。
结果
中位随访 40.0 个月后，D-Vd 组患者的中位 PFS 长于 Vd 组，标准风险（16.6 与 6.6 个月；HR，0.26；95%CI，0.19-0.37；P<0.0001）和高风险（12.6 与 6.2 个月；HR，0.41；95%CI，0.21-0.83；P=0.0106）患者。无论细胞遗传学风险如何，D-Vd 均能实现深度应答，包括更高的 MRD 阴性率和持续的 MRD 阴性率。安全性与 CASTOR 的总体人群一致。
结论
这些更新的数据强化了达雷妥尤单抗为基础的方案治疗 RRMM 的有效性和耐受性，无论细胞遗传学风险状态如何。
试验注册
ClinicalTrials.gov，NCT02136134。注册日期：2014 年 5 月 12 日。
Zotero 插件