一项有关来那度胺联合低剂量地塞米松治疗中国复发/难治性多发性骨髓瘤患者的多中心、开放性Ⅱ期临床试验:MM-021试验(全译文)

A multicenter,open-label,phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma:the MM-021 trial

目的：在中国,复发/难治性多发性骨髓瘤（RRMM）的治疗方案不能满足患者的需求。来那度胺联合低剂量地塞米松可有效治疗白种人RRMM患者,并且通常具备良好的耐受性,但是过去的研究并未评估该疗法对中国RRMM患者的疗效。方法：MM-021是一项多中心、单治疗组、开放性Ⅱ期临床试验,旨在评估来那度胺联合低剂量地塞米松治疗中国RRMM患者的疗效、安全性和药物代谢动力学特征。既往接受过≥1种抗骨髓瘤疗法治疗的患者服用来那度胺＋低剂量地塞米松,直至疾病进展或停止用药。存活患者需在入选后接受≥1年的随访。来那度胺剂量为25mg/d,并根据基线肾功能进行调整。大多数受试者均为晚期病患（85.6%为Durie-SalmonⅢ期）,并且既往接受过大量治疗（56.7%既往接受过≥4种抗骨髓瘤治疗;69.5%既往接受过沙利度胺治疗;63.1%既往接受过硼替佐米治疗）;5.3%患者为免疫球蛋白D型（IgD）。结果：安全性研究群体共有199例入选患者。在疗效研究群体187例患者中,疾病控制率（至少疾病稳定）为94.7%,总缓解率（至少部分缓解）为47.6%,患有肾功能损害及IgD型的患者亦取得高缓解率。至15.2个月中位随访期后,中位缓解持续时间为8.8（0.4-18.8）个月,中位无进展生存期为8.3个月（95%CI6.5-9.8）。最常见3-4级不良事件（AE）为贫血（26.1%）、中性粒细胞减少（25.1%）、血小板减少（14.6%）、肺炎（13.1%）、白细胞减少（9.5%）和中性粒细胞计数减少（8.5%）。AE导致40.2%的患者减少来那度胺剂量和（或）暂停使用,并导致约9.0%的患者停止用药。来那度胺药物代谢动力学特征与白种人和日本患者报道的结果相似。结论：既往接受过多次治疗的中国RRMM患者（包括肾功能损害和IgD亚型患者）对来那度胺联合低剂量地塞米松治疗方案具有可接受的安全性和高缓解率。这些研究发现显示了此治疗方案对于目前治疗方案均无效的中国RRMM患者具有临床应用潜力。

Objective：There is an unmet need for treatment options in Chinese patients with relapsed or refractory multiple myeloma（RRMM）.Lenalidomide plus low-dose dexamethasone is effective and generally well tolerated in Caucasian RRMM patients,but no previous study has evaluated this regimen in Chinese RRMM patients.Method：MM-021 is a phase 2,multicenter,single-arm open-label registration trial conducted to assess the efficacy,safety,and pharmacokinetics of lenalidomide plus low-dose dexamethasone in Chinese patients with RRMM.Patients with≥1prior antimyeloma therapy received lenalidomide plus low-dose dexamethasone until disease progression or discontinuation.Follow-up of surviving patients continued for≥1year after enrollment.The lenalidomide dose was 25mg/d,and was adjusted according to baseline renal function.Most patients had advanced disease（85.6%had Durie-Salmon stageⅢ）and were heavily pretreated（56.7%had received≥4prior regimens;69.5%prior thalidomide and 63.1% prior bortezomib）;5.3% had immunoglobulin D（IgD）disease.Result：The safety population comprised 199 eligible patients.In the 187 efficacy population,the disease control rate（at least stable disease）was 94.7%,and the overall response rate（at least partial response）was 47.6%.High response rates were also achieved in patients who had renal impairment and in those with IgD disease.After a median study follow-up of 15.2months,the median response duration was 8.8（0.4to 18.8）months and median progression-free survival was 8.3months（95%CI6.5to 9.8）.The most common grade 3to 4adverse events（AEs）were anemia（26.1%）,neutropenia（25.1%）,thrombocytopenia（14.6%）,pneumonia（13.1%）,leucopenia（9.5%）,and decreased neutrophil count（8.5%）.AEs led to lenalidomide dose reduction and/or interruption in 40.2% patients,and treatment discontinuation in about 9.0% patients.The pharmacokinetic profile of lenalidomide was similar to that reported in Caucasian and Japanese patients.Conclusion：Lenalidomide plus low-dose dexamethasone is associated with a high response rate and acceptable safety profile in heavily pretreated Chinese patients with RRMM,including those with renal impairment and IgD subtype.These findings highlight the clinical potential of this regimen in Chinese RRMM patients who have exhausted current treatment options.