Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA.
Clin Lymphoma Myeloma Leuk. 2023 Sep;23(9):687-696. doi: 10.1016/j.clml.2023.05.004. Epub 2023 May 6.
Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone demonstrated superior progression-free survival (PFS) but directionally different overall survival (OS) favoring pomalidomide (hazard ratio [HR], 1.10) in OCEAN.
These analyses further investigated prognostic subgroups impacting survival in updated data from the randomized, phase 3 OCEAN study (NCT03151811; date: February 3, 2022) and the phase 2 HORIZON study (NCT02963493; date: February 2, 2022).
In OCEAN, subgroups prognostic for OS were age (P = .011; <65 years favored pomalidomide) and no previous autologous stem cell transplant (ASCT) or progression >36 months after ASCT (P = .001; favored melflufen). Overall, 245 of 495 (49%) patients randomized had received a previous ASCT, of which 202 (82%) had progressed within 36 months following their ASCT. When excluding patients who had progressed <36 months post-ASCT (melflufen group, n = 145; pomalidomide group, n = 148), median OS was 23.6 months with melflufen and 19.8 months with pomalidomide (HR, 0.83 [95% CI, 0.62-1.12]; P = .22). Among patients with triple-class refractory disease in HORIZON, patients who had progressed <36 months post-ASCT (n = 58) had a lower response rate and shorter duration of response and PFS than the remaining patients (n = 52). Safety was consistent with previous reports.
These analyses demonstrate a consistent benefit for melflufen and dexamethasone in patients with relapsed/refractory multiple myeloma who have not received an ASCT or progressed >36 months after receiving an ASCT (ClinicalTrials.gov identifier: NCT03151811).
美法仑氟苯酰胺（melflufen）是一种首创的烷化肽药物偶联物，加用地塞米松在 OCEAN 研究中显示出优越的无进展生存期（PFS），但总生存期（OS）呈方向性差异，对泊马度胺有利（风险比[HR]，1.10）。
这些分析进一步研究了影响更新后的随机、3 期 OCEAN 研究（NCT03151811；日期：2022 年 2 月 3 日）和 2 期 HORIZON 研究（NCT02963493；日期：2022 年 2 月 2 日）中生存预后的亚组。
在 OCEAN 中，预后 OS 的亚组包括年龄（P=.011；<65 岁的患者中，泊马度胺更有利）和无既往自体干细胞移植（ASCT）或 ASCT 后 36 个月以上的进展（P=.001；美法仑更有利）。总体而言，495 名随机分组的患者中有 245 名（49%）接受了既往 ASCT，其中 202 名（82%）在 ASCT 后 36 个月内进展。当排除 ASCT 后<36 个月进展的患者（美法仑组 n=145；泊马度胺组 n=148）时，美法仑的中位 OS 为 23.6 个月，泊马度胺为 19.8 个月（HR，0.83[95%CI，0.62-1.12]；P=.22）。在 HORIZON 中具有三重耐药性的患者中，ASCT 后<36 个月进展的患者（n=58）的反应率、缓解持续时间和 PFS 均低于其余患者（n=52）。安全性与之前的报告一致。
这些分析表明，在未接受 ASCT 或 ASCT 后 36 个月以上进展的复发性/难治性多发性骨髓瘤患者中，美法仑和地塞米松治疗具有一致的获益（ClinicalTrials.gov 标识符：NCT03151811）。
