Real-world comparison of daratumumab-based regimens in relapsed/refractory multiple myeloma using health record data

Benjamin A. Derman , Jacob Ambrose , Laura L. Fernandes , Christina M. Zettler , Eric Hansen , Andrew J. Belli , Ching-Kun Wang
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Abstract

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.

利用健康记录数据对基于达拉单抗的复发性/难治性多发性骨髓瘤治疗方案进行真实世界比较
摘要基于达拉单抗(dara)的三联疗法常用于复发性/难治性多发性骨髓瘤(RRMM)的二线(2L)和三线(3L)治疗,通常与地塞米松和硼替佐米(dara-Vd)、卡非佐米(dara-Kd)或泊马度胺(dara-Pd)联合使用。据我们所知,我们首次进行了真实世界(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,使用的是 COTA 的 rw 数据库,研究对象是使用 dara-Vd、dara-Kd 或 dara-Pd 开始 2L 或 3L 治疗的 MM 患者。采用 Kaplan-Meier 法分析了 rw 下次治疗时间 (rwTTNT) 和 rw 总生存期 (rwOS)。比较分析采用修剪的逆治疗概率加权法,以控制潜在的混杂因素。共有639名患者接受了以达拉为基础的2L或3L治疗方案(达拉-Vd,n = 201;达拉-Kd,n = 122;达拉-Pd,n = 316)。高比例患者患有功能性(52%)或细胞遗传学(26%)高危疾病;49%为来那度胺难治性患者。dara-Vd 的中位 rwTTNT 为 7.6 个月,dara-Kd 为 12.9 个月(危险比 [HR],0.70;95% 置信区间 [CI],0.49-0.99)。同样,达拉-Vd 的中位 rwTTNT 为 6.9 个月,达拉-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)。没有一种方案的rwOS更优。在接受2L或3L达拉三联疗法的RRMM患者中,与达拉-Kd和达拉-Pd相比,达拉-Vd的rwTTNT较差。
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