目的 观察达雷妥尤单抗联合来那度胺及地塞米松(DRd)方案巩固治疗序贯达雷妥尤单抗和来那度胺两药维持治疗1例高龄高危初治多发性骨髓瘤患者的疗效、生存时间和不良反应。方法 回顾分析广州市第一人民医院老年病科血液肿瘤科2019年3月收治的1例高龄高危初治多发性骨髓瘤患者的临床资料,并复习相关最新文献。结果 患者应用伊沙佐米、来那度胺和地塞米松方案诱导治疗13疗程后只达到部分缓解的疗效,未能进一步缓解,且不良反应多且严重,后改为DRd方案巩固治疗2疗程后,达到完全缓解,继续使用达雷妥尤单抗联合来那度胺两药维持治疗,不良反应少,至随访结束总生存期和无进展生存期均为35个月。结论 含达雷妥尤单抗方案巩固和维持治疗可能会改善高龄高危初治多发性骨髓瘤患者的预后,延长生存时间,耐受性好。

Objective To observe the efficacy, survival time and adverse reactions of daratumumab combined with lenalidomide and dexamethasone (DRd) in the consolidation treatment of sequential daratumumab and lenalidomide maintenance treatment of an elderly patient with high-risk newly diagnosed multiple myeloma. Methods The clinical data of the elderly patient with newly diagnosed multiple myeloma treated in the Department of Geriatrics, Hematology & Oncology Ward, Guangzhou First People's Hospital in March 2019 were retrospectively analyzed, and the relevant latest literatures were reviewed. Results After 13 courses of induction treatment with isazomib, lenalidomide and dexamethasone, it only achieved partial remission, but failed to further remission, and there were many serious adverse reactions.Later, it was changed to DRd therapy to consolidate treatment.After 2 courses of treatment, it achieved complete remission.After that, we continued to use daratumumab combined with lenalidomide for maintenance treatment, with few adverse reactions.At the time of submission, the overall survival and progression free survival were 35 months. Conclusions Consolidation and maintenance therapy with daratumumab may improve the prognosis, prolong survival time and with good tolerance in elderly patients with high-risk newly diagnosed multiple myeloma.

目的 探讨PAD方案治疗初发多发性骨髓瘤(MM)有效性及安全性。方法 统计54例接受PAD方案治疗的初发MM患者临床资料,采用回顾性分析方法。PAD方案:P(硼替佐米)1.3 mg/m²,第1、4、8、11天皮下注射,A(脂质体阿霉素)25～30 mg/m²,第1天静脉滴注,D(地塞米松)40 mg,第1～4 天静脉滴注或口服,每21天为1个疗程。采用IMWG疗效标准判定疗效,按NCICTCAE(第3版)标准判断不良反应。结果 ①总体疗效:平均4(2~8)个疗程后,47例(87.0%)患者获部分缓解(PR)以上疗效,其中完全缓解(CR)20例(37.0%),很好的部分缓解(VGPR)19例(35.2%),部分缓解(PR)8例(14.9%),疾病稳定(SD)5例(9.3%),病情进展率(PD)2例(3.7%)。②亚组疗效:54例患者中,35例治疗4个以上疗程,19例小于4个疗程,ORR分别为97.1%(34/35)、68.4%(13/19)(P=0.003)。按照年龄、肾功能、骨破坏数目、骨髓浆细胞比例、ALB、LDH、β2-MG、细胞遗传学、ISS分期、临床分型进行队列亚组疗效比较,结果提示亚组疗效差异无统计学意义(P＞0.05);③总体安全性:中性粒细胞减少8例(14.8%),血小板减少8例(14.8%),周围神经病变16例(29.6%),腹泻2例(3.7%),便秘2例(3.7%),带状疱疹4例(7.4%),细菌感染5例(9.3%),以上不良反应经对症治疗后症状减轻或消失。④亚组安全性:按照年龄和疗程数进行亚组比较,年龄大于60岁患者和年龄小于60岁患者总不良反应发生率和3/4级不良反应发生率分别是47.4% vs 60.0% 和15.8% vs 20.1%,(P=0.404和P=1.00);治疗4个以上疗程患者和小于4个疗程患者总不良反应发生率和3/4级不良反应发生率分别是57.9% vs 54.3%和21.2% vs 17.1%,(P=1.00和P=0.728)。结论 PAD方案治疗初发MM效果显著,缓解率和疗程数有相关性,疗效与传统的生存预后因素无关,可作为MM诱导治疗的一线方案。脂质体阿霉素心脏毒性小,替代传统蒽环类药物阿霉素,不良反应可控,耐受性良好,更适用于老年MM患者。

Objective To investigate the efficacy and safety of PAD regimen in previously untreated patients with multiple myeloma(MM). Methods We retrospectively analyzed 54 patients with newly-diagnosed MM,who were treated with PAD regimen: Bortezomib 1.3mg/m² subcutaneously on day 1,4,8,11. Liposomal doxorubicin 25～30 mg/m² intravenously on the first day. Dexamethasone 40 mg/d intravenously or orally on days 1～4. Treatment was repeated every 21 days. Response was evaluated according to the International Uniform Response Criteria for MM.Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria,version 3.0. Results ①Overall response:after median 4(2～8) courses of PAD,47patients(87.0%)responsed,including complete response (CR) in 20 (37.0%),very good partial response (VGPR) in 19 (35.2%),partial response (PR) in 8 (14.9%),stable disease (SD) in 5 (9.3%) and progressive disease (PD) in 2 (3.7%). ②Subgroups efficacy: among the 54 patients,35 patients received more than 4 therapeutic courses,and 19 patients received less than 4 courses.The ORR was 97.1% (34/35) and 68.4% (13/19) respectively (P=0.003). Subgroups efficacy were compared according to age,renal function,number of bone destruction,proportion of bone marrow plasma cells,ALB,LDH,β2-MG,cytogenetics,ISS staging and clinical classification. The results indicated that there was no statistical difference(P>0.05). ③Overall safety: adverse events included neutropenia in 8 (14.8%),thrombocytopenia in 8 (14.8%),peripheral neuropathy in 16 (29.6%),diarrhea in 2 (3.7%),constipation in 2 (3.7%),herpes zoster in 4 (7.4%) and bacterial infection in 5 (9.3%). The adverse events relieved or disappeared after symptomatic treatment. ④Subgroups safety: compared by age and courses of treatment,the incidence of overall adverse events and grade 3/4 adverse events in patients older than 60 years and ones younger than 60 were 47.4% vs 60.0% and 15.8% vs 20.1% respectively,(P=0.404,P=1.00). The incidence of overall adverse events and grade 3/4 adverse events in patients with more than 4 therapeutic courses and ones with less than 4 courses were 57.9% vs 54.3% and 21.2% vs 17.1% respectively,(P=1.00和P=0.728). Conclusion PAD regimen has really curative effect in treating patients with newly diagnosed MM. There is a correlation between remission rate and therapeutic courses. It can be used as the first selected protocol for the induction therapy of MM. Its efficacy is independent of traditional prognostic factors.Liposomal doxorubicin has almost no cardiotoxicity. Replacing traditional anthracycline doxorubicin,the adverse events are controllable and the tolerance is generally well. PAD regimen is more proper to be applied to older patients with MM.