Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy
Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy
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DOI：
10.1038/s41375-019-0435-7
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发表时间：
2019-09-01
期刊：
影响因子：
11.4
通讯作者：
Costa, Luciano J.
中科院分区：
文献类型：
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作者：
Gandhi, Ujjawal H.;Cornell, Robert F.;Costa, Luciano J.
CD 38靶向单克隆抗体（CD 38 MoAB）、达雷妥尤单抗和isatuximab的引入显著影响了多发性骨髓瘤（MM）患者的管理。尚未描述CD 38 MoAB难治性MM患者的结局。我们分析了来自14个学术中心的275名患有CD 38 MoAB难治性疾病的MM患者的结局。MM诊断与CD 38 MoAB（T-0）无效之间的中位间隔为50.1个月。整个队列的中位总生存期（OS）为8.6 [95% CI]。7.5-9.9]个月，范围从免疫调节剂（IMiD）和蛋白酶体抑制剂（PI）不同时难治的患者的11.2个月至“五难治性”患者（CD 38 MoAB、2种PI和2种IMiD难治性）的5.6个月。249例（90%）患者在T-0后至少采用了一种后续治疗方案。T-0后第一方案的总体缓解率为31%，中位无进展生存期（PFS）和OS分别为3.4和9.3个月。卡非佐米和烷化剂联合治疗（中位5.7个月）以及达雷妥尤单抗和IMiD联合治疗（中位4.5个月）最能实现PFS。CD 38 MoAB难治性MM患者预后不良，本研究为在该人群中测试新疗法提供了基准。
The introduction of CD38-targeting monoclonal antibodies (CD38 MoABs), daratumumab and isatuximab, has significantly impacted the management of patients with multiple myeloma (MM). Outcomes of patients with MM refractory to CD38 MoABs have not been described. We analyzed outcomes of 275 MM patients at 14 academic centers with disease refractory to CD38 MoABs. Median interval between MM diagnosis and refractoriness to CD38 MoAB (T-0) was 50.1 months. The median overall survival (OS) from T o for the entire cohort was 8.6 [95% C.I. 7.5-9.9] months, ranging from 11.2 months for patients not simultaneously refractory to an immunomodulatory (IMiD) agent and a proteasome inhibitor (PI) to 5.6 months for "pentarefractory" patients (refractory to CD38 MoAB, 2 PIs and 2 IMiDs). At least one subsequent treatment regimen was employed after T-0 in 249 (90%) patients. Overall response rate to first regimen after T-0 was 31% with median progression-free survival (PFS) and OS of 3.4 and 9.3 months, respectively. PFS was best achieved with combinations of carfilzomib and alkylator (median 5.7 months), and daratumumab and IMiD (median 4 5 months). Patients with MM refractory to CD38 MoAB have poor prognosis and this study provides benchmark for new therapies to be tested in this population.