Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma
Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma
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DOI：
10.1182/blood-2017-03-775122
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发表时间：
2017-09-07
期刊：
影响因子：
20.3
通讯作者：
Singh, Zeba
中科院分区：
文献类型：
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作者：
Badros, Ashraf;Hyjek, Elizabeth;Singh, Zeba
程序性死亡1(PD-1)受体及其配体(PD-L1)促进多发性骨髓瘤(MM)的免疫逃避。我们推测，pembrolizumab，PD-1抗体，可以增强泊马度胺产生的抗骨髓瘤细胞免疫，导致改善临床反应。在这项单中心的第二阶段研究中，48名复发/难治性多发性骨髓瘤(RRMM)患者接受培溴利珠单抗28天一周期的治疗，每两周静脉注射200毫克，泊马度胺每天4毫克，共21天，地塞米松每周40毫克。患者平均接受3条治疗路线(范围2-5)，中位年龄(35-83岁)，同时接受免疫调节药物和蛋白酶体抑制剂治疗：(35[73%])对两者都无效；(31[70%])接受过自体移植，(30[62%])有高危细胞遗传学。48例患者中有19例(40%)发生了3至4级的不良反应，包括血液毒性(19例[40%])、高血糖(12例[25%])和肺炎(7例[15%])。自身免疫事件包括肺炎(6[13%])和甲状腺功能减退(5[10%])，主要是
Programmed death 1 (PD-1) receptor and its ligand (PD-L1) facilitate immune evasion in multiple myeloma (MM). We hypothesized that pembrolizumab, PD-1-antibody, can enhance antimyeloma cellular immunity generated by pomalidomide, leading to improved clinical responses. In this single-center, phase 2 study, 48 patients with relapsed/refractory MM (RRMM) received 28-day cycles of pembrolizumab, 200 mg IV every 2 weeks, pomalidomide 4 mg daily for 21 days, and dexamethasone 40 mg weekly. Patients had a median of 3 (range: 2-5) lines of therapy, median age 64 (range: 35-83) years, and had received both an immune modulatory drug (IMiD) and proteasome inhibitor: (35 [73%] of 48) were refractory to both; (31 [70%]) had received an autologous transplant, and (30 [62%]) had high-risk cytogenetics. Adverse events grade 3 to 4 occurred in (19 [40%] of 48 patients), including hematologic toxicities (19 [40%]), hyperglycemia (12 [25%]), and pneumonia (7 [15%]). Autoimmune events included pneumonitis (6 [13%]) and hypothyroidism (5 [10%]), mostly