Objective: To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM). Methods: It was a prospective, multi-center, observational study. A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015. Relevant information was recorded, such as baseline clinical data, cytogenetic abnormalities, treatment regimens, and duration of treatment, safety, and survival. Results: (1)There were 126 relapsed and refractory MM (RRMM) patients, 25 newly diagnosed patients and 19 maintenance patients. The evaluable RRMM patients accounted for 120 cases, among which 74 cases(61.7%) reached the partial response (PR) or above, and a very good partial response (VGPR) in 16 patients (13.3%), a complete response (CR) in 14 cases (11.7%), a strictly complete response (sCR) in 4 cases (3.3%). Thus, a VGPR or above in 34 patients accounted for 28.3%. (2)The median follow-up was 13 months, the median time to progression 12 months. The median survival after receiving lenalidomide was 19 months, and the median overall survival (OS) was 62 months. (3) The univariate analysis in 120 RRMM patients suggested that prognostic factors for significant improvement in PFS included normal karyotype, international staging system (ISS) Ⅰ-Ⅱ, t(4; 14) negative (detected by fluorescence in situ hybridization), non-bortezomib resistance and response to previous regimens. As to OS, non-bortezomib resistance, response to previous regimens and non-primary refractoriness were positive factors. Multivariate analysis showed that the response to previous regimens (PR or better) was an independent good prognostic factor for progress-free survival(PFS), non-bortezomib resistance and non-primary refractoriness for OS. (4) Grade 3 or 4 adverse events that occurred in more than 10% of all enrolled patients were neutropenia (12.7%), leukocytosis(11.5%) and thrombocytopenia (12.7%). Owing to intolerance of toxic side effects, 7 cases withdrew lenalidomide. Conclusions: No matter what combination, regimens containing lenalidomide are effective to RRMM patients with overall response rate 61.7%, a time to progression 12 months and an overall survival 62 months.The toxicity is quite tolerable and manageable. In addition, the response to previous treatment (reached PR or above) is the independent good prognostic factor for PFS, non-bortezomib resistance and non-primary refractoriness for OS. Clinical trail registration: Clinicaltrials.gov, NCT01947309.
目的： 本研究针对接受来那度胺治疗的中国多发性骨髓瘤(MM)成年患者，基于真实世界研究模式，针对当前中国真实的临床情况进行整体分析，以评价来那度胺对中国MM患者真实的效益、风险和治疗价值。 方法： 本研究是一项前瞻性、多中心、非干预性临床研究，累计入选了来自国内12家医院2013年6月—2015年11月期间连续收治的165例接受来那度胺治疗的MM患者。所有入选者的用药方案均由主管医生决定。记录项目包括基线资料、细胞遗传学、治疗方案和疗程、安全性及生存等。 结果： (1)复发/难治性MM(RRMM)患者共计126例，初治MM患者有25例，维持治疗MM有19例。RRMM中可行疗效评估者达到120例，其总体有效率为61.7%；其中16例(13.3%)达非常好的部分缓解，14例(11.7%)为完全缓解，4例(3.3%)为严格意义的完全缓解，因此达非常好的部分缓解及以上的患者占28.3%。(2)对120例RRMM中位随访13个月，其总体中位无进展生存(PFS)期为12个月，应用来那度胺后的中位生存期为19个月，中位总体生存(OS)期为62个月。(3)单因素分析结果显示：染色体核型正常(G显带)、国际分期体系(ISS)分期为Ⅰ～Ⅱ期、荧光免疫杂交检测t(4；14)阴性、来那度胺治疗前未出现硼替佐米耐药、最佳疗效达部分缓解(PR)及其以上是应用来那度胺后PFS预后良好因素，来那度胺治疗前未出现硼替佐米耐药、最佳疗效达PR及其以上、非原发耐药是OS预后良好的因素。多因素分析结果显示：最佳疗效达PR及其以上水平是PFS预后良好的独立因素；而非原发耐药、来那度胺治疗前未出现硼替佐米耐药对OS具有独立预后意义。(4)165例患者均纳入不良反应事件统计范围内，其中在≥3级的副作用中，白细胞减少19例(11.5%)，血小板减少21例(12.7%)，而中性粒细胞减少达21例(12.7%)，最终有7例患者因药物毒副作用停药。 结论： 选择不同的含来那度胺的联合方案，在RRMM患者中总体有效率可达61.7%，PFS期达12个月，OS期达62个月，且药物毒性反应可耐受。最佳疗效达PR及其以上水平是PFS预后良好的独立因素，而非原发耐药、来那度胺治疗前未出现硼替佐米耐药对OS具有独立预后意义。 临床试验注册： 美国临床试验数据库，注册号NCT01947309.
Keywords: Lenalidomide; Multiple myeloma; Real world study.