Abstract：
Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone demonstrated superior progression-free survival (PFS), but not overall survival (OS), versus pomalidomide plus dexamethasone in relapsed/refractory multiple myeloma in the OCEAN study. Time to progression (TTP) <36 months after a prior autologous stem cell transplantation (ASCT) was a negative prognostic factor for OS with melflufen. This post hoc exploratory analysis evaluated patients refractory to prior alkylators (e.g., cyclophosphamide and melphalan) in OCEAN. In 153 patients refractory to prior alkylators (melflufen, n = 78; pomalidomide, n = 75), the melflufen and pomalidomide arms had similar median PFS (5.6 months [95% CI, 4.2-8.3] vs. 4.7 months [95% CI, 3.1-7.3]; hazard ratio [HR], 0.92 [95% CI, 0.63-1.33]) and OS (23.4 months [95% CI, 14.4-31.7] vs. 20.0 months [95% CI, 12.0-28.7]; HR, 0.92 [95% CI, 0.62-1.38]). Among alkylator-refractory patients with a TTP ≥ 36 months after a prior ASCT or no prior ASCT (melflufen, n = 54; pomalidomide, n = 53), the observed median PFS and OS were longer in the melflufen arm than the pomalidomide arm. The safety profile of melflufen was consistent with previous reports. These results suggest that melflufen is safe and effective in patients with alkylator-refractory disease, suggesting differentiated activity from other alkylators.
摘要：
美法仑氟灭酰胺（美氟芬），一类中的烷化肽-药物缀合物，加地塞米松表现出优越的无进展生存期（PFS），但不是总生存率（OS），在OCEAN研究中，与泊马度胺联合地塞米松治疗复发/难治性多发性骨髓瘤的比较。先前自体干细胞移植（ASCT）后进展时间（TTP）<36个月是美氟芬OS的负面预后因素。这项事后探索性分析评估了对先前的烷化剂难治的患者(例如，环磷酰胺和美法仑）在海洋中。在153名对先前的烷化剂（美氟芬，n=78；泊马度胺，n=75),美氟芬和泊马度胺组的中位PFS相似（5.6个月[95％CI，4.2-8.3]与4.7个月[95%CI，3.1-7.3]；危险比[HR]，0.92[95%CI，0.63-1.33]）和OS（23.4个月[95%CI，14.4-31.7]与20.0个月[95%CI，12.0-28.7]；HR，0.92[95%CI，0.62-1.38]）。在先前ASCT后TTP≥36个月或先前无ASCT（美氟芬，n=54；泊马度胺，n=53),美氟芬组观察到的中位PFS和OS长于泊马度胺组.美氟芬的安全性与以前的报告一致。这些结果表明，美氟芬在偏烷因子难治性疾病患者中是安全有效的，表明与其他烷化剂的活性不同。
