Objective: To investigate the efficacy and safety of daratumumab in relapsed/refractory multiple myeloma (RRMM) patients. Methods: Fifty-two RRMM patients treated with daratumumab from September 2019 to November 2021 in West China Hospital were retrospectively enrolled, including 31 males and 21 females. The mean age of these patients at the first diagnosis of multiple myeloma was (58±10) years. According to the dosage of daratumumab, patients were divided into low dosage group (n=10) and high dosage group (n=42). Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse event rates were investigated. Univariate and multivariate analysis of potential factors were conducted. Results: Of the 52 patients, 8 received daratumumab monotherapy, 27 received daratumumab plus immuno-modulatory drug (IMiD) treatment, 4 received daratumumab plus proteosome inhibitor (PI) treatment, and 11 received daratumumab plus dexamethasone treatment. The diagnosis age of high dosage group patients was (57±9) years, which was significantly younger than that of low dosage group [(66±10) years] (P=0.009). The baseline creatinine level of high dosage group patients [M (Q1, Q3)] was 91 (68, 196) μmol/L, which was significantly higher than that of low dosage group [66 (51, 76) μmol/L] (P=0.021). There was no significant difference in other baseline clinical characteristics, previous treatment regimens, previous lines of treatment, and regimen and cycles of daratumumab between the high dosage group and low dosage group (all P>0.05). The ORR for the 52 patients was 71.2% (37/52). The ORR for daratumumab plus IMiD group was 81.5% (22/27), which was significantly higher than that in monotherapy or dexamethasone group [ORR: 52.6% (10/19), P=0.036). With a median follow-up [M (Q1, Q3)] of 7 (5, 26) months, the median PFS for overall cohort was 17 (95%CI: 9.6-24.4) months. The median PFS for daratumumab plus IMiD group was 26 (95%CI: 6.0-46.0) months, which was significantly better than that in monotherapy or dexamethasone group [12 (95%CI: 3.5-20.5) months] (HR=0.231, 95%CI: 0.075-0.715, P=0.011). Higher diagnosis age was the risk factor of progression (HR=1.085, 95%CI: 1.016-1.158, P=0.014), while more cycles of daratumumab treatment was the protective factor of progression (HR=0.669, 95%CI: 0.495-0.904, P=0.009). There was no significant influence of daratumumab dosage on progression (high dosage vs low dosage, HR=1.016, 95%CI: 0.221-4.668, P=0.984). The median OS for overall cohort was 26 (95%CI: 13.1-38.9) months. Higher serum calcium was the independent risk factor of death (HR=12.190, 95%CI: 1.170-127.048, P=0.037). There was no significant influence of daratumumab dosage on death (high dosage vs low dosage, HR=0.818, 95%CI: 0.171-3.917, P=0.802). Adverse events included infections (43.2%, 16/37), infusion-associated reactions (29.7%, 11/37), and thrombocytopenia (27.0%, 10/37). Conclusions: Daratumumab is effective to treat RRMM. The dosage of daratumumab has no significant influence on prognosis when used in combined treatment. The incidence of adverse events is relatively low, with a favorable safety profile.
目的： 探讨达雷妥尤单抗治疗复发难治性多发性骨髓瘤（RRMM）患者的有效性及安全性。 方法： 回顾性纳入四川大学华西医院2019年9月至2021年11月行达雷妥尤单抗治疗的52例RRMM患者，其中男31例，女21例，初次诊断为多发性骨髓瘤（MM）时年龄为（58±10）岁。根据达雷妥尤单抗治疗剂量，将患者分为低剂量组（n=10）和高剂量组（n=42）。统计分析患者总缓解率（ORR）、无进展生存时间（PFS）、总生存时间（OS）以及不良反应发生率，并对影响患者预后的因素进行单因素及多因素分析。 结果： 52例患者中，8例行达雷妥尤单抗单药治疗，27例联合免疫调节剂（IMiD）治疗，4例联合蛋白酶体抑制剂（PI）治疗，2例联合IMiD和PI治疗，11例联合地塞米松治疗。高剂量组患者初次诊断为MM时年龄为（57±9）岁，小于低剂量组（66±10）岁（P=0.009）；高剂量组患者的基线肌酐水平M（Q1，Q3）为91（68，196）μmol/L，高于低剂量组的66（51，76）μmol/L（P=0.021）；两组患者在其余基线临床特征、既往治疗方案及线数、达雷妥尤单抗治疗方案及疗程差异均无统计学意义（均P>0.05）。52例患者总体ORR为71.2%（37/52），IMiD联合治疗组ORR为81.5%（22/27），高于单用或联合地塞米松治疗组的52.6%（10/19）（P=0.036）。随访时间M（Q1，Q3）为7（5，26）个月，总体中位PFS为17（95%CI：9.6~24.4）个月，IMiD联合治疗组中位PFS为26（95%CI：6.0~46.0）个月，显著高于单用或联合地塞米松治疗组的12（95%CI：3.5~20.5）个月（HR=0.231，95%CI：0.075~0.715，P=0.011）。初次诊断为MM时年龄高是疾病进展的危险因素（HR=1.085，95%CI：1.016~1.158，P=0.014），达雷妥尤单抗疗程数更多是疾病进展的保护因素（HR=0.669，95%CI：0.495~0.904，P=0.009）；达雷妥尤单抗剂量对疾病进展无影响（以低剂量为参照，HR=1.016，95%CI：0.221~4.668，P=0.984）。总体中位OS为26（95%CI：13.1~38.9）个月，血钙高是患者死亡的危险因素（HR=12.190，95%CI：1.170~127.048，P=0.037）；达雷妥尤单抗剂量对患者死亡无影响（以低剂量为参照，HR=0.818，95%CI：0.171~3.917，P=0.802）。常见不良事件为感染（43.2%，16/37）、输液相关不良反应（29.7%，11/37）、血小板减少（27.0%，10/37）。 结论： 达雷妥尤单抗治疗RRMM效果较好，在联合治疗时的剂量对预后无影响；患者不良反应发生率较低、安全可控。.