多发性骨髓瘤患者早期复发对疗效和生存的影响及早期复发危险因素分析

Effect of early relapse on the therapeutic efficacy and survival for patients with multiple myeloma and analysis of risk factors of early relapse

目的探讨早期复发多发性骨髓瘤(MM)患者的疗效和预后以及发生早期复发的影响因素。方法回顾性分析2018年1月至2021年1月在河北大学附属医院收治的164例新诊断MM患者资料,至随访结束,53例(32.3%)复发。根据复发时间是否在12个月内分为早期复发组与晚期复发组,比较两组患者的临床特征、总有效率(ORR)及总生存(OS)。采用logistic回归分析患者年龄、性别、清蛋白、乳酸脱氢酶(LDH)、β_(2)⁃微球蛋白(β_(2)⁃MG)、血红蛋白、血肌酐、血钙、骨髓浆细胞比例、髓外病变、高危荧光原位杂交(FISH)等是否为早期复发的影响因素。根据已发表的基于7个临床试验构建的简化的MM早期复发(S⁃ERMM)评分系统对复发患者进行分组,比较早期复发和晚期复发患者危险度构成差异。结果164例新诊断MM患者中位随访26个月(12~48个月)。53例复发MM患者中,24例早期复发,29例晚期复发。早期复发组患者一线治疗时ORR较晚期复发组降低[70.8%(17/24)比89.7%(26/29),χ^(2)=3.04,P=0.001]。早期复发组中位OS时间较晚期复发组缩短(24个月比未达到,P<0.001),初始诱导治疗时最佳疗效≥完全缓解(CR)、≥非常好的部分缓解(VGPR)及≥部分缓解(PR)的早期复发患者OS均较晚期复发组差,差异均有统计学意义(P值分别为0.008、0.011、0.012)。多因素logistic回归分析结果显示,清蛋白低(<35 g/L比≥35 g/L:OR=1.644,95%CI 1.076~2.511,P=0.022)及高LDH(<正常值上限比≥正常值上限:OR=0.998,95%CI 0.985~1.011,P=0.030)是早期复发的独立影响因素。24例早期复发患者中,S⁃ERMM评分系统低危、中危、高危组分别有5例(20.8%)、13例(54.2%)、6例(25.0%);29例晚期复发患者中,分别有18例(62.1%)、9例(31.0%)、2例(6.9%),早期复发组和晚期复发组间S⁃ERMM评分系统危险度分布差异有统计学意义(χ^(2)=9.09,P=0.003)。结论早期复发MM患者疗效和预后不佳,且预后不受一线治疗缓解程度影响。低清蛋白及高LDH可能是MM患者早期复发的独立危险因素。

Objective To investigate the therapeutic efficacy and prognosis of multiple myeloma(MM)patients with early relapse and the influencing factors of early relapse.Methods The clinical data of 164 patients with newly diagnosed MM admitted to Affiliated Hospital of Hebei University from January 2018 to January 2021 were retrospectively analyzed,and 53 cases(32.3%)relapsed at the end of the follow⁃up.According to the recurrence within 12 months or not,the patients were divided into early relapse group and advanced relapse group;the clinical characteristics,overall response rate(ORR)and overall survival(OS)of both groups were compared.Logistic regression was used to analyze if the following indexes including age,gender,albumin,lactate dehydrogenase(LDH),β_(2)⁃microglobulin(β_(2)⁃MG),hemoglobin,creatinine,serum calcium,bone marrow plasma cell ratio,extramedullary disease,high⁃risk fluorescent in situ hybridization(FISH)were the influencing factors of the early relapse.Based on 7 published clinical trials,simplified early relapse MM(S⁃ERMM)scoring system was constructed to subgroup all relapsed patients.The difference in risk stratification between early relapsed patients and advanced relapsed patients was compared.Results The median follow⁃up time of 164 newly diagnosed MM patients was 26 months(12-48 months).Among 53 relapsed MM patients,24 cases had early relapse and 29 cases had advanced relapse.The ORR of patients with early relapse was decreased compared with that of those with advanced relapse[70.8%(17/24)vs.89.7%(26/29),χ^(2)=3.04,P=0.001].The median OS of the early relapse group was shorter than that of the advanced relapse group(24 months vs.not reached,P<0.001).The OS of patient in the early relapse group with the best response≥complete remission(CR),≥very good partial remission(VGPR)and≥partial remission(PR)during initial induction therapy was worse than that of those in the advanced relapse group,and the differences were statistically significant(P values were 0.008,0.011,0.012,respectively).Multivariate Logistic regression analysis showed low albumin(<35 g/L vs.≥35 g/L:OR=1.644,95%CI 1.076-2.511,P=0.022)and high LDH(<the upper limit of normal value vs.≥the upper limit of normal value:OR=0.998,95%CI 0.985-1.011,P=0.030)were independent influencing factors of early relapse.Among 24 early relapse patients,there were 5 cases(20.8%),13 cases(54.2%),6 cases(25.0%),respectively in the S⁃ERMM scoring system low⁃risk,middle⁃risk,high⁃risk groups;among 29 advanced relapse patients,there were 18 cases(62.1%),9 cases(31.0%),2 cases(6.9%),respectively in the S⁃ERMM scoring system low⁃risk,middle⁃risk,high⁃risk groups;the difference in risk stratification of the S⁃ERMM scoring system between the early relapse group and the advanced relapse group was statistically significant(χ^(2)=9.09,P=0.003).Conclusions MM patients with early relapse have poor therapeutic efficacy and prognosis.The prognosis is not affected by the depth of remission to first⁃line therapy.Low albumin and high LDH may be independent risk factors of MM patients with early relapse.