Derman Benjamin A, Ambrose Jacob, Fernandes Laura L, Zettler Christina M, Hansen Eric, Belli Andrew J, Wang Ching-Kun
Section of Hematology/Oncology, University of Chicago, Chicago, IL.
COTA, Inc, New York, NY.
Blood Neoplasia. 2024 Feb 15;1(1):100003. doi: 10.1016/j.bneo.2024.100003. eCollection 2024 Mar.
Daratumumab (dara)-based triplet therapies are commonly used in the second-line (2L) and third-line (3L) settings in relapsed/refractory multiple myeloma (RRMM), usually in combination with dexamethasone and either bortezomib (dara-Vd), carfilzomib (dara-Kd), or pomalidomide (dara-Pd). We performed a real-world (rw) analysis to directly compare these regimens, to our knowledge, for the first time. This was an observational, retrospective cohort study using COTA's rw database of patients with MM who have initiated 2L or 3L therapy with dara-Vd, dara-Kd, or dara-Pd. rw time to next treatment (rwTTNT) and rw overall survival (rwOS) were analyzed using the Kaplan-Meier method. Comparative analyses were conducted using a trimmed inverse probability of treatment weighting method to control for potential confounders. A total of 639 patients received a dara-based regimen as either 2L or 3L therapy (dara-Vd, n = 201; dara-Kd, n = 122; and dara-Pd, n = 316). A high proportion had functional (52%) or cytogenetic (26%) high-risk disease; 49% were lenalidomide refractory. Median rwTTNT for dara-Vd was 7.6 months and was 12.9 months for dara-Kd (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.49-0.99). Similarly, median rwTTNT for dara-Vd was 6.9 months and 15.3 months for dara-Pd (HR, 0.57; 95% CI, 0.43-0.77). Median rwTTNT for dara-Pd was 15.7 months, and for dara-Kd 13.2 months (HR, 1.1; 95% CI, 0.8-1.6). No regimen was associated with superior rwOS. Among patients with RRMM receiving 2L or 3L therapy with a dara-based triplet, dara-Vd was associated with inferior rwTTNT compared with both dara-Kd and dara-Pd. dara-Vd may not be a suitable control arm for most phase 3 studies.
基于达雷妥尤单抗（dara）的三联疗法常用于复发/难治性多发性骨髓瘤（RRMM）的二线（2L）和三线（3L）治疗，通常与地塞米松联合使用，以及硼替佐米（dara-Vd）、卡非佐米（dara-Kd）或泊马度胺（dara-Pd）。据我们所知，我们首次进行了一项真实世界（rw）分析，以直接比较这些治疗方案。这是一项观察性、回顾性队列研究，使用COTA的rw数据库中开始使用dara-Vd、dara-Kd或dara-Pd进行2L或3L治疗的MM患者。使用Kaplan-Meier方法分析rw至下次治疗时间（rwTTNT）和rw总生存期（rwOS）。使用修剪后的治疗加权逆概率方法进行比较分析，以控制潜在的混杂因素。共有639例患者接受了基于dara的方案作为2L或3L治疗（dara-Vd，n = 201；dara-Kd，n = 122；dara-Pd，n = 316）。很大一部分患者患有功能性（52%）或细胞遗传学（26%）高危疾病；49%对来那度胺难治。dara-Vd的中位rwTTNT为7.6个月，dara-Kd为12.9个月（风险比[HR]，0.70；95%置信区间[CI]，0.49-0.99）。同样，dara-Vd的中位rwTTNT为6.9个月，dara-Pd为15.3个月（HR，0.57；95%CI，0.43-0.77）。dara-Pd的中位rwTTNT为15.7个月，dara-Kd为13.2个月（HR，1.1；95%CI，0.8-1.6）。没有一种方案与更好的rwOS相关。在接受基于dara的三联疗法进行2L或3L治疗的RRMM患者中，与dara-Kd和dara-Pd相比，dara-Vd的rwTTNT较差。对于大多数3期研究，dara-Vd可能不是一个合适的对照臂。
