免疫麻痹对达深度缓解新诊断多发性骨髓瘤患者预后的意义

Prognostic significance of immunoparesis in newly diagnosed multiple myeloma patients who achieved deep response

目的评价新诊断多发性骨髓瘤(NDMM)患者达最佳缓解后的免疫状态对疾病进展的影响。方法本研究回顾性分析了2015年8月至2020年2月北京朝阳医院确诊的经治疗达非常好的部分缓解(VGPR)及以上疗效的125例NDMM患者资料,主要包括患者诱导及巩固治疗后最佳缓解达到深度缓解(≥VGPR)时免疫麻痹状态及恢复情况,结合患者一般资料、遗传学等因素,分析以上因素对疾病无进展生存期(PFS)的影响。结果(1)全部患者均接受了新药治疗,50.4%(63/125)完成了自体干细胞移植。全部患者最佳缓解均为VGPR及以上,达完全缓解(CR)者为89.6%,达CR且微小残留病(MRD)(二代流式MRD)阴性者为66.4%。(2)Cox多因素分析显示重度免疫麻痹持续3个月、持续6个月均是NDMM患者PFS独立预后不良因素。(3)达最佳缓解时,重度免疫麻痹组3年PFS率明显低于非重度免疫麻痹组(41.3%比64.4%,P=0.021)。(4)重度免疫麻痹持续3个月、持续6个月组,其3年PFS率显著低于非持续重度免疫麻痹组(30.0%比63.5%,P<0.001;16.4%比63.8%,P<0.001)。(5)获得CR且MRD阴性者,重度免疫麻痹持续6个月组3年PFS率明显低于非持续重度免疫麻痹组(22.2%比83.2%,P=0.005)。结论NDMM达深度缓解后的免疫状态与预后相关,此时仍存在重度免疫麻痹及持续重度免疫麻痹预示疾病早期进展。

Objective To evaluate the effect of immune status on disease progression in patients with newly diagnosed multiple myeloma(NDMM)achieving deep response.Methods Clinical data of 125 NDMM patients at Beijing Chaoyang Hospital from August 2015 to February 2020 were retrospectively analyzed who achieved very good partial response(VGPR)or better after front-line treatment.The immune status and its influence on progression-free survival(PFS)were analyzed.Results(1)All patients received novel drug regimens,and 50.4%(63/125)patients followed by autologous stem cell transplantation(ASCT).The rate of complete response(CR)as best efficacy was 89.6%,in which 66.4%achieved CR and MRD negativity tested by second generation flow cytometry.(2)Cox multivariate analysis suggested that persistent severe immunoparesis 3 months and 6 months since the best response was an independent poor prognostic factor for PFS.(3)The 3-year PFS rate in the severe immunoparesis group was significantly lower than that in the control group(41.3%vs.64.4%,P=0.021).(4)The 3-year PFS rates in patients with persistent severe immunoparesis at 3 months or 6 months were significantly lower(30.0%vs.63.5%,P<0.001;16.4%vs.63.8%,P<0.001 respectively).(5)Even in those achieving CR and negative MRD,the 3-year PFS rate when severe immunoparesis lasted 6 months was significantly lower(22.2%vs.83.2%,P=0.005).Conclusion The immune status in NDMM patients achieving deep response is closely related to survival.Persistent severe immunoparesis indicates early progression of the disease.