IgD型多发性骨髓瘤临床特征、新药治疗效果及预后分析

Analysis of clinical characteristics of IgD multiple myeloma and effect of novel agents on prognosis of patients

目的探讨IgD型多发性骨髓瘤(multiple myeloma,MM)患者的临床特征、治疗、生存及预后影响因素。方法回顾性分析2013年6月至2021年9月复旦大学附属中山医院血液科收治的25例IgD型MM患者的病例资料。分析患者的基线特征、实验室检查及细胞遗传学指标;根据国际骨髓瘤工作组(International Myeloma Working Group,IMWG)诊断标准评估疗效。采用Kaplan-Meier方法进行生存分析,采用log-rank检验进行单因素分析,将P<0.15的变量纳入多因素Cox回归分析。结果25例IgD型MM患者中男性17例(68%),21例(84%)年龄低于65岁,λ轻链型24例(96%);DS分期Ⅲ期21例(84%),国际分期系统(International Staging System,ISS)分期Ⅲ期12例(48%);荧光原位杂交(fluorescence in situ hybridization,FISH)结果显示77.3%(17/22)患者存在细胞遗传学异常,以1q21扩增(14例,63.6%)和IgH重排(9例,40.9%)多见。25例患者均使用含蛋白酶体抑制剂(proteasome inhibitors,PIs)的化疗方案,可评价疗效者20例,总反应率(overall response rate,ORR)达95%,其中完全缓解(complete remission,CR)率和严格意义CR(sCR)率占50%;移植与未移植组的CR+sCR分别为66.7%(6/9)和36.4%(4/11)。25例患者中位总生存期(overall survival,OS)和无进展生存期(progression free survival,PFS)分别为46.7个月和25.3个月;移植组与未移植组中位PFS分别为46.7个月和21.6个月(P=0.018)。含硼替佐米和来那度胺2种新药的VRD(硼替佐米+来那度胺+地塞米松)方案比仅含硼替佐米的VCD(硼替佐米+环磷酰胺+地塞米松)方案的OS及PFS更长。血清乳酸脱氢酶和肌酐升高是影响患者OS和PFS的不良因素。结论IgD型MM以λ轻链为主,多见于65岁以下男性,初诊时常合并高危细胞遗传学异常;PIs等新药的应用可改善IgD型MM的预后,同时新药时代下自体造血干细胞移植仍可发挥一定作用。

Objective To explore the clinical characteristics,treatment,survival,and prognostic factors of patients with IgD multiple myeloma(MM).Methods Clinical data of 25 patients with IgD MM admitted into the Zhongshan Hospital,Fudan University from June 2013 to September 2021 were analyzed.Baseline characteristics,laboratory tests,and cytogenetic features of patients were collected.Clinical efficacy was evaluated according to International Myeloma Working Group(IWMG)criteria.Survival analysis was performed by Kaplan-Meier curves;univariate analysis was performed using Log-rank test,and variables with P<0.15 were included in multivariate Cox regression analysis.Results Among the 25 patients with IgD MM,21 cases(68%)were male,with 21 cases(84%)younger than 65 years old.24 patients(96%)of IgD MM were ofλlight chain type.21 patients(84%)were in DS-Ⅲstage and 12 patients(48%)were in ISS-Ⅲstage.FISH results showed that 77.3%(17/22)of patients had cytogenetic abnormalities.Among them,14 cases(63.6%)complicated with 1q21 amplification and 9 cases(40.9%)with IgH rearrangement,being the most common abnormalities.All patients were treated with chemotherapy regimens containing proteasome inhibitors.The total overall response rate(ORR)was 95%in 20 efficacy-evaluable patients with complete remission(CR)and stringent CR(sCR)rate accounting for 50%,with 66.7%(6/9)and 36.4%(4/11)achieving CR and sCR in patients with and without ASCT,respectively.The median overall survival(OS)and progression-free survival(PFS)were 46.7 months and 25.3 months in all patients.The median PFS in the transplanted and non-transplanted arms were 46.7 and 21.6 months,respectively(P=0.018).Bortezomib and lenalidomide-contained regimen(VRD)resulted in longer OS and PFS than single novel agent regimen of bortezomib(VCD).Elevated lactate dehydrogenase and creatinine levels were adverse prognostic factors associated with OS and PFS.Conclusions IgD MM is dominated byλlight chain and more commonly happened in men,younger than 65 years old,and often identified at diagnosis with high-risk cytogenetic abnormalities.The availability of novel agents such as proteasome inhibitors(PIs)can improve the efficacy and prognosis of IgD MM,and autologous stem cell transplantation can still play a role in the era of new agents.