【摘要】 目的 探讨真实世界中含达雷妥尤单抗(Dara)三药方案治疗多发性骨髓瘤(MM)的有效性和安全性。方法 回顾性分析2020年11月至2024年6月河南科技大学第一附属医院、河南省肿瘤医院、河南省人民医院收治的使用含Dara三药方案的61例MM患者的临床资料。基于细胞遗传学危险度分层和既往用药情况的个体化治疗方案：DVd(Dara+硼替佐米+地塞米松)、DRd(Dara+来那度胺+地塞米松)、DPd(Dara+泊马度胺+地塞米松)、DKd(Dara+卡非佐米+地塞米松)及DId(Dara+伊沙佐米+地塞米松)方案。Dara给药方案为16 mg/kg静脉输注，初始阶段(第1～8周)每周1次，第9～24周每两周1次，维持期(24周后)每4周1次，每4次给药为1个疗程。根据中国多发性骨髓瘤指南(2022年修订)的疗效标准进行评估，采用美国国家癌症研究所常见不良反应术语评定标准5.0版评估不良反应。根据随访数据分析接受Dara治疗者的总生存期(OS)和无进展生存期(PFS)。结果 61例MM患者中DVd组19例(31.1%)、DRd组18例(29.5%)、DPd组18例(29.5%)、DKd组3例(4.9%)和DId组3例(4.9%),总体缓解率达81.9%(50/61),达到的最佳疾病缓解程度为严格意义上的完全缓解4.9%(3例)、完全缓解37.7%(23例)、非常好的部分缓解21.3%(13例)、部分缓解18.0%(11例)、微小缓解6.6%(4例)、疾病稳定8.2%(5例)和疾病进展3.3%(2例)。经过中位15.1个月(范围1.4～32.5个月)的随访，30个月总生存率为81.4%,30个月无进展生存率为58.6%,中位OS和PFS均未达到。年龄<65岁与≥65岁MM患者的PFS生存曲线比较，差异无统计学意义(P=0.398);一线组、二线组、三线及以上组MM患者的PFS生存曲线比较，差异有统计学意义(P<0.001);DVd、DPd、DRd三种方案患者的PFS生存曲线比较，差异无统计学意义(P=0.487)。含Dara三药方案对于干细胞的采集及血细胞的重建无明显影响，对合并淀粉样变性的MM患者有较好疗效。结论 Dara在MM患者中疗效较好，安全性可控，可改善患者预后，延长患者生存时间。更多还原

【Abstract】 Objective To explore the efficacy and safety of daratumumab(Dara)-based triplet regimens in the treatment of multiple myeloma(MM) in the real-world setting. Methods A retrospective analysis was conducted on the clinical data of 61 MM patients treated with Dara-based triplet regimens at the First Affiliated Hospital of Henan University of Science and Technology, Henan Cancer Hospital, and Henan Provincial People’s Hospital from November 2020 to June 2024. Based on cytogenetic risk and treatment history, Dara-based regimens included DVd, DRd, DPd, DKd, and DId, combining it with bortezomib, lenalidomide, pomalidomide, carfilzomib, or ixazomib, all with dexamethasone. The administration regimen for Dara was 16 mg/kg via intravenous infusion, with an initial phase(weeks 1-8) of weekly dosing, followed by biweekly dosing in weeks 9-24, and a maintenance phase(after week 24) of dosing every 4 weeks. Each cycle consisted of 4 doses. Treatment efficacy was evaluated according to the response criteria outlined in the Chinese Guidelines for the Diagnosis and Management of Multiple Myeloma(2022 Revision), while adverse reactions were assessed using the National Cancer Institute’s Common Terminology Criteria for Adverse Events, version 5.0. Follow-up data were analyzed to determine the overall survival(OS) and progression-free survival(PFS) of patients receiving Dara-based therapy. Results Among the 61 MM patients, the distribution across treatment groups was as follows: DVd group(19 cases, 31.1%), DRd group(18 cases, 29.5%), DPd group(18 cases, 29.5%), DKd group(3 cases, 4.9%), and DId group(3 cases, 4.9%). The overall response rate reached 81.9%(50/61). The best achieved disease responses were stringent complete response in 4.9%(3 cases), complete response in 37.7%(23 cases), very good partial response in 21.3%(13 cases), partial response in 18.0%(11 cases), minimal response in 6.6%(4 cases), stable disease in 8.2%(5 cases), and disease progression in 3.3%(2 cases). After a median follow-up of 15.1 months(range: 1.4-32.5 months), the 30-month OS rate was 81.4%, and the 30-month PFS rate was 58.6%. The median OS and PFS were not yet reached. The PFS curves showed no significant difference between MM patients aged <65 years and those ≥65 years(P=0.398). However, a statistically significant disparity was observed among patients receiving first-line, second-line, and third-line or higher treatments(P<0.001). In contrast, no significant variation in PFS was found across the DVd, DPd, and DRd treatment regimens(P=0.487). The Dara-based triple-drug regimen shows no significant impact on stem cell collection or hematopoietic reconstitution, while demonstrating favorable efficacy in MM patients with concomitant amyloidosis. Conclusion Dara demonstrates favorable efficacy and manageable safety in MM patients, improving clinical outcomes and prolonging survival.更多还原