以硼替佐米为基础的诱导治疗后序贯自体造血干细胞移植治疗多发性骨髓瘤临床分析

Bortezomib-based induction therapy followed by autologous hematopoietic stem cell transplantation in multiple myeloma

目的 评估硼替佐米序贯移植方案对多发性骨髓瘤（MM）患者的短期疗效和长期疗效,从而找出适合移植患者的最佳治疗方法.方法 回顾性分析白2006年6月1日至2014年1月30日在我院诊断并接受含硼替佐米诱导方案序贯大剂量马法兰化疗联合自体造血干细胞移植（ASCT）的100例MM患者资料.结果 100例患者在诱导后、移植后及巩固维持治疗后的总有效率分别为90.0％、97.0％和98.9％.中位无进展生存（PFS）期为42.3个月,中位总生存（OS）期尚未达到.轻链型MM患者在2个疗程后、非轻链型在4个疗程后继续增加疗程数,累积的≥接近完全缓解（nCR）率将没有明显增加.在初治患者中,轻链型MM采用VD方案或PAD方案诱导治疗后,累积≥nCR率接近;对于非轻链型MM,PAD方案疗效优于VD方案.早期移植组的中位PFS期长于晚期移植组（50.7个月比26.6个月,P=0.023）.骨髓移植组的中位PFS期长于外周血造血干细胞移植组（“尚未达到”比36.1个月,P=0.049）.移植后无论是否获得完全缓解（CR）,均可从维持治疗中获益.在各阶段（诱导后、移植后、维持后）获得CR患者的中位PFS期均长于仅获得nCR的患者.结论 含硼替佐米化疗方案诱导后序贯移植是合适移植MM患者的首选治疗方案,不同M蛋白类型患者需要的诱导方案和诱导疗程数有所不同.无论ASCT后是否获得CR,维持治疗均可使患者获益.诱导后即获得CR及ASCT后持续CR患者预示更好的长期生存.

Objective To evaluate the short-term and long-term effect of novel agents followed by autologous hematopoietic stem cell （ASCT） in Chinese multiple myeloma（MM） patients in order to find out the optimal therapeutic regimen for transplant-eligible patients.Methods Clinical data of 100 active MM patients receiving bortezomib-based induction regimens followed by high-dose melphalan and ASCT were retrospectively analyzed from June 1,2006 to January 30,2014.Results The overall response rates （ORR） after induction therapy,transplantation and consolidation and maintenance therapy were respectively 90.0%,97.0%,and 98.9%.The median progress free survival （PFS） was 42.3 months.The median overall survival（OS） was not reached.The cumulative near complete response （nCR） ＋ complete respanse （CR） rate was no longer improved after 4 cycles of induction therapy for non-light chain type MM and two cycles for light-chain type.In newly-diagnosed light-chain type MM patients,the cumulative nCR ＋ CR rate after 4 cycles of bortezomib plus dexamethasone （VD） regimen was similar to that of bortezomib,doxorubicin and dexamethasone （PAD）.While for those non-light-chain types,three drug-based regimen was better than two drug-based.PFS of patients receiving early ASCT was longer than that of late ASCT （50.7 months vs 26.6 months,P =0.023）.PFS in patients receiving autologous bone marrow stem cell transplantation （ABMSCT） was longer than that of autologous peripheral blood stem cell transplantation （APBSCT） （NAvs 36.1 months,P =0.049）.Maintenance therapy was beneficial regardless of the response rate after ASCT.Patients with CR at any time during the therapy had longer PFS than those with nCR.Conclusions Bortezomib-based therapy followed by ASCT is the first line therapy for transplant-eligible MM patients.Patients with different types of M protein require different induction regimens.Maintenance is beneficial to patients after ASCT,no matter whether a CR is reached or not.Patients with CR after induction or ASCT tend to have longer survival.