含小剂量硼替佐米的三药联合方案治疗老年多发性骨髓瘤的临床研究

Three-Drug Combination Regimen Containing Low-Dose Bortezomib in the Treatment of Elderly Multiple Myeloma

目的:探讨含小剂量硼替佐米的三药联合方案治疗老年多发性骨髓瘤的临床疗效。方法:选取2016年9月至2019年12月于该院就诊的老年(年龄≥60岁)多发性骨髓瘤患者100例,根据用药方案随机分为观察组(49例)和对照组(51例)。两组患者均给予硼替佐米、沙利度胺(100 mg/d,第1—28日口服)和地塞米松(20 mg/d,第1—2、4—5、8—9和11—12日给药);其中观察组患者的方案为硼替佐米0.7 mg/m^(2),第1、4、8和11日给药;对照组患者的方案为硼替佐米1.3 mg/m^(2),第1、4、8和11日给药。1个疗程为28 d。比较两组患者治疗前、治疗3个疗程后的血常规、免疫功能、胸苷激酶1(TK1)及乳酸脱氢酶(LDH)水平,比较临床疗效、不良反应发生情况和远期生存指标的差异。结果:治疗后,两组患者血清CD4+T细胞、自然杀伤细胞水平较治疗前明显升高,CD8+T细胞及调节性T细胞水平较治疗前明显降低,骨髓瘤细胞、TK1及LDH水平较治疗前明显降低,差异均有统计学意义(P<0.05);治疗后,两组患者上述指标水平比较,差异均无统计学意义(P>0.05)。观察组患者的总有效率为46.94%(23/49),对照组的为60.78%(31/51),两组的差异无统计学意义(P=0.228)。两组患者总生存率的差异无统计学意义(P>0.05);但观察组患者出现带状疱疹、周围神经病和胃肠道反应等不良反应的发生率更低,与对照组比较,差异有统计学意义(P<0.05)。结论:含小剂量硼替佐米的三药联合方案治疗老年多发性骨髓瘤患者的临床效果与标准剂量硼替佐米的三药联合方案相当,而周围神经病、胃肠道反应等不良反应发生率明显降低,且能明显改善患者血常规、免疫功能,降低肿瘤负荷,安全性更高。

OBJECTIVE:To explore the clinical efficacy of three-drug combination regimen containing low-dose bortezomib in the treatment of elderly multiple myeloma.METHODS:A total of 100 elderly patients(≥60 years)with multiple myeloma admitted into our hospital from Sept.2016 to Dec.2019 were randomly divided into the observation group(n=49)and the control group(n=51)according to different medication regimen.Both groups were given bortezomib,thalidomide(100 mg/d,orally,from the 1st to the 28th day)and dexamethasone(20 mg/d,from the 1st to the 2nd,4th to 5th,8th to 9th,and 11th to 12th day).The observation group was given bortezomib 0.7 mg/m^(2) on the 1st,4th,8th and 11th day,while the control group received bortezomib 1.3 mg/m^(2) on the 1st,4th,8th and 11th day.One course of treatment was 28 d.Blood routine,immune function,thymidine kinase 1(TK1)and lactate dehydrogenase(LDH)levels were compared between two groups before treatment and after treatment of 3 courses.Differences of clinical efficacy,occurrence of adverse drug reactions and long-term survival indicators were compared.RESULTS:After treatment,the levels of serum CD4+T cells and natural killer cells in two groups were significantly higher than those before treatment,the levels of CD8+T cells and Treg cells were significantly lower than those before treatment,and the levels of myeloma cells,TK1 and LDH were significantly lower than those before treatment,the differences were statistically significant(P<0.05);there was no significant difference between two groups after treatment(P>0.05).The total effective rate of the observation group was 46.94%(23/49),and that of the control group was 60.78%(31/51),with no statistically significant difference(P=0.228).There was no significant difference in overall survival rate between two groups(P>0.05).However,the incidence of adverse drug reactions such as herpes zoster,peripheral neuropathy and gastrointestinal reactions was lower in the observation group,and the difference was statistically significant compared with the control group(P<0.05).CONCLUSIONS:Compared with the standard dose of bortezomib,the three-drug combination regimen containing low-dose bortezomib has similar clinical effects in the treatment of elderly multiple myeloma,and the incidence of adverse drug reactions such as peripheral neuropathy and gastrointestinal reactions decrease significantly,and can significantly improve the blood routine,immune function,reduce the tumor burden with higher safety.