中性粒细胞与淋巴细胞比值对BCD方案在初治多发性骨髓瘤患者中治疗反应影响的分析

Analysis of the effect of neutrophil-lymphocyte ratio on response to BCD regimen for newly diagnosed multiple myeloma

目的:探索诊断时中性粒细胞与淋巴细胞比值(NLR)对BCD(硼替佐米+环磷酰胺+地塞米松)治疗方案在初治多发性骨髓瘤(MM)中治疗反应的影响。方法:对2018年9月—2020年8月在深圳大学总医院接受BCD方案治疗的53例初治MM进行回顾性分析。根据NLR的中位数,将患者分为高NLR组27例(NLR≥2.60,H-NLR组)和低NLR组26例(NLR<2.60,L-NLR组),对2组患者的临床特点、治疗反应和无进展生存期(PFS)进行分析。结果:53例患者的中位年龄为61岁,中位PFS为10.9个月。H-NLR组患者的β2微球蛋白水平明显高于L-NLR组[(23.30±35.85)mg/L vs(6.87±6.34)mg/L,P<0.05];H-NLR组中β2微球蛋白≥5.5 mg/L的比例为62.96%,明显高于L-NLR组的34.62%(P<0.05);H-NLR组患者中肌酐水平和肾功能衰竭的比例显著高于L-NLR组患者(P<0.05)。此外,尽管H-NLR组患者中合并高钙血症患者的比例与L-NLR组比较差异无统计学意义,但H-NLR组患者的血钙水平显著高于L-NLR组患者,差异有统计学意义(P<0.05)。单因素分析显示,H-NLR组患者的PFS显著低于L-NLR组(9.20个月vs 11.63个月,P<0.05),特别是H-NLR组中未获得非常好的部分缓解以上治疗反应(≥VGPR)患者的PFS显著低于L-NLR组中未获得≥VGPR患者(6.47个月vs 10.80个月,P<0.05)。此外,患者治疗后实现≥VGPR和不伴有遗传学异常患者的PFS显著延长。在含有VGPR和遗传学异常的多因素分析显示,H-NLR作为接受BCD方案治疗的初治MM患者的预后不良影响依然存在(HR 3.76,95%CI 1.67~8.44,P<0.05)。患者未获得≥VGPR治疗反应复发的风险也显著增加(HR 3.23,95%CI 1.45~7.22,P<0.05)。结论:接受BCD方案治疗的H-NLR组MM患者的PFS较L-NLR组明显下降,这在未获得≥VGPR的H-NLR患者中更为明显,NLR是反映BCD方案在初治MM患者治疗效果的独立预后因素。

Objective:To investigate the effect of the ratio of neutrophil to lymphocyte(NLR)on the response of BCD(bortezomib+cyclophosphamide+dexamethasone)therapy in newly diagnosed multiple myeloma(MM).Methods:We retrospectively analyzed 53 cases of newly diagnosed MM treated with BCD regimen in Shenzhen University General Hospital from September 2018 to August 2020.According to the median of NLR,the patients were divided into H-NLR group(NLR≥2.60,27 cases)and L-NLR group(NLR<2.60,26 cases).The clinical characteristics,treatment response and progression-free survival(PFS)of the two groups were analyzed.Results:The median age of 53 patients with MM was 61 years and the median PFS was 10.9 months.The level of beta-2 microglobulin in H-NLR group was significantly higher than that in L-NLR group([23.30±35.85]mg/L vs[6.87±6.34]mg/L,P<0.05).The proportion of beta 2 microglobulin(>5.5 mg/L)in H-NLR group was significantly higher than that in L-NLR group(62.96%vs 34.62%,P<0.05).The creatinine level and the proportion of renal failure in H-NLR group were significantly higher than those in L-NLR group(P<0.05).In addition,although the proportion of patients with hypercalcemia in the H-NLR group was not significantly different from that in the L-NLR group,the serum calcium level in the H-NLR group was significantly higher than that in the L-NLR group,and the difference was statistically significant(P<0.05).Univariate analysis showed that the PFS of H-NLR group was significantly lower than that of L-NLR group(9.20 months vs 11.63 months,P<0.05).Especially in H-NLR group,the PFS of patients who did not receive a very good partial response after treatment(≥VGPR)was significantly lower than that of patients who did not receive≥VGPR in L-NLR group(6.47 months vs 10.80 months,P<0.05).In addition,patients achieved≥VGPR and patients without genetic abnormalities had significantly prolonged PFS.Multivariate analysis including VGPR and genetic abnormalities showed that the adverse prognostic effects of H-NLR on MM patients treated with BCD regimen were still present(HR 3.76,95%CI 1.67-8.44,P<0.05).The risk of recurrence was also significantly increased in patients who did not get treatment response of≥VGPR(HR 3.23,95%CI 1.45-7.22,P<0.05).Conclusion:The PFS of MM patients in H-NLR group treated with BCD regimen is significantly lower than that in L-NLR group,which is more obvious in H-NLR patients without VGPR.NLR is an independent prognostic factor reflecting the therapeutic effect of BCD regimen in newly treated MM patients.