泊马度胺联合低剂量地塞米松治疗中国复发/难治性多发性骨髓瘤患者的有效性和安全性：一项多中心、前瞻性、单臂、Ⅱ期临床试验。
Efficacy and safety of pomalidomide and low-dose dexamethasone in Chinese patients with relapsed or refractory multiple myeloma: a multicenter, prospective, single-arm, phase 2 trial.
机构信息
Department of Hematology, Changzheng Hospital, Shanghai, China.
Department of Hematology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
出版信息
BMC Cancer. 2022 Jul 1;22(1):722. doi: 10.1186/s12885-022-09802-y.
BACKGROUND
Pomalidomide in combination with dexamethasone has demonstrated positive results in patients with relapsed or refractory multiple myeloma (RRMM), but no data are available in China. We conducted a multicenter, single-arm trial to examine the efficacy and safety of bioequivalent generic pomalidomide plus low-dose dexamethasone in Chinese RRMM patients.
METHODS
Adult (≥ 18 years of age) RRMM patients who progressed after at least two previous treatments, including bortezomib and lenalidomide, were eligible. Pomalidomide was given orally at 4 mg/day on days 1 to 21 of a 28-day cycle. Dexamethasone was given at 40 mg/day (either orally or intravenously; 20 mg/day at 75 years or older) on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression or intolerable adverse events (AEs). The primary end point was objective response rate (ORR).
RESULTS
Seventy-four patients were enrolled between February 2017 and February 2019. All patients had progressed within 60 days of their last therapy. 74.3% of the patients were resistant to lenalidomide, 31.1% had renal insufficiency and 33.8% had high-risk cytogenetic RRMM. The median follow-up duration was 33.0 months (range 31.1-34.8 months). The ORR was 37.8% in the overall analysis, 32.7% in lenalidomide-refractory patients, 36.0% in patients with high-risk cytogenetics and 34.8% in RRMM patients with renal impairment. The median progression-free survival was 5.7 months (95% CI 3.7-8.8 months). The median overall survival was 24.3 months (95% CI 14.4-41.1 months). The most common grade 3 and 4 treatment-emergent adverse events (TEAEs) were neutropenia (63.5%), leukopenia (37.8%), thrombocytopenia (28.4%), and anemia (31.1%). Pulmonary infection (27.0%) was the most frequent grade 3 and 4 nonhematologic TEAE. No previously unreported AEs were observed. No venous thromboembolism was reported.
CONCLUSIONS
Pomalidomide in combination with low-dose dexamethasone is effective and safe in Chinese RRMM patients.
TRIAL REGISTRATION
The study is registered at Chinese Clinical Trial Registry (ChiCTR) ( ChiCTR-OIC-17013234 , first registered on 03/11/2017).
背景
泊马度胺联合地塞米松在复发/难治性多发性骨髓瘤（RRMM）患者中显示出积极的结果，但在中国尚无相关数据。我们开展了一项多中心、单臂试验，以评估生物等效仿制药泊马度胺联合小剂量地塞米松在接受过至少两种治疗（包括硼替佐米和来那度胺）的中国 RRMM 患者中的疗效和安全性。
方法
入组标准为年龄≥18 岁，RRMM 患者，至少在接受两种治疗后进展，包括硼替佐米和来那度胺。泊马度胺在每个 28 天周期的第 1 至 21 天口服 4mg/天。地塞米松在每个周期的第 1、8、15 和 22 天给药，剂量为 40mg/天（口服或静脉注射；75 岁及以上患者为 20mg/天）。治疗持续至疾病进展或不可耐受的不良反应（AE）。主要终点为客观缓解率（ORR）。
结果
2017 年 2 月至 2019 年 2 月期间共纳入 74 例患者。所有患者在末次治疗后 60 天内均出现疾病进展。74.3%的患者对来那度胺耐药，31.1%的患者存在肾功能不全，33.8%的患者存在高危细胞遗传学 RRMM。中位随访时间为 33.0 个月（范围 31.1-34.8 个月）。总体分析的 ORR 为 37.8%，来那度胺耐药患者的 ORR 为 32.7%，高危细胞遗传学患者的 ORR 为 36.0%，肾功能不全的 RRMM 患者的 ORR 为 34.8%。中位无进展生存期为 5.7 个月（95%CI：3.7-8.8 个月）。中位总生存期为 24.3 个月（95%CI：14.4-41.1 个月）。最常见的 3 级和 4 级治疗相关不良事件（TEAE）是中性粒细胞减少症（63.5%）、白细胞减少症（37.8%）、血小板减少症（28.4%）和贫血（31.1%）。肺部感染（27.0%）是最常见的 3 级和 4 级非血液学 TEAE。未观察到以前未报告的 AE。无静脉血栓栓塞报告。
结论
泊马度胺联合小剂量地塞米松在中国 RRMM 患者中具有疗效和安全性。
试验注册
本研究在中国临床试验注册中心（ChiCTR）（ChiCTR-OIC-17013234，首次注册于 2017 年 3 月 11 日）进行注册。
Zotero 插件