去甲基化药物联合Venetoclax与半量预激类方案治疗老年初诊急性髓系白血病的疗效比较

Comparison of Therapeutic Efficacy between Hypomenthylating Agents Combined with Venetoclax and Half Dose Priming Regimen in Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia

目的:比较去甲基化药物(HMA)联合Venetoclax(VEN)方案与HMA联合半量预激类(CAG-like)方案治疗不适合接受强化疗的老年初诊急性髓系白血病患者的临床疗效及安全性。方法:回顾性分析苏州大学附属第一医院2019年4月至2020年10月43例初诊不适合接受强化疗的老年急性髓系白血病患者的临床资料,16例接受HMA-VEN方案治疗,27例接受HMA-CAG-like方案治疗。比较两组患者的缓解率、早期死亡率及生存情况,并根据HCT-CI评分分组,比较不同分组中两种不同方案对患者疗效及生存的影响,进一步对患者预后进行分析。结果:治疗1个疗程后,HMA-VEN组和HMA-CAG-like组的总缓解率分别为81.3%(13/16)和51.9%(14/27),比较差异具有统计学意义(χ^(2)=4.650,P=0.045)。HMA-VEN组的中位生存时间尚未达到,HMA-CAG-like组中位生存时间为11.2个月,HMA-VEN组老年急性髓系白血病患者有较长的总生存期(OS)(P=0.055)。两组患者均无肿瘤溶解综合征发生,其主要不良反应为消化道反应、骨髓抑制和感染。HMA-VEN组粒细胞缺乏性感染、肺部感染、血小板输注量显著低于HMA-CAG-like组(P<0.05),而两组粒细胞缺乏时间、红细胞输注量相当(P>0.05)。HMA-VEN组早期死亡1例,HMA-CAG-like组因肺部感染、呼吸衰竭、脑出血、肺泡出血等早期死亡8例,死亡率显著高于HMA-VEN组(P=0.043)。在全部患者中,HCT评分0-2分组和≥3分组的OS比较有显著性统计学差异(P=0.033)。将HMA-CAG-like组患者以HCT评分分组,评分≥3分组有着更差的预后(P=0.01),而HMA-VEN组以HCT评分分组的两组间预后比较无统计学差异(P=0.681)。在0-2分组中,接受HMA-VEN方案的患者9例、HMA-CAG-like方案的患者22例,两者OS比较无统计学意义(P=0.281);而在≥3分组中,接受HMA-VEN方案的患者7例、HMA-CAG-like方案的患者5例,接受HMA-VEN方案的患者有着更长的OS(P=0.015)。结论:Venetoclax联合HMA能够获得更高的治疗反应率、更低的早期死亡率以及更长的总生存期,尤其是在患者合并症多、耐受性差的情况之下。

Objective:To compare the clinical efficacy and safety of hypomenthylating agents(HMA)combined with Venetoclax(VEN)and half dose priming regimen(CAG-like)in the treatment of elderly patients with newly diagnosed acute myeloid leukemia(AML)who were not suitable for intensive chemotherapy.Methods:The clinical data of 43 newly diagnosed elderly patients with AM L who were not suitable for intensive chemotherapy in our hospital from April 2019 to October 2020 were retrospectively analyzed.Among them,16 cases received HM A-VEN regimen and 27 cases received HM A-CAG-like regimen.The remission rate,early mortality and survival were compared between the two groups.And,the patients were grouped according to HCT-CI score.The effects of two different regimens in different groups on the efficacy and survival of patients were compared,and the prognosis of patients was further analyzed.Results:After one course of treatment,the total remission rate of HM A-VEN group and HM A-CAG-like group was 81.3%(13/16)and 51.9%(14/27),respectively,and the difference between the two groups was statistically significant(χ^(2)=4.650,P=0.045).The median overall survival(OS)time of HM A-VEN group had not yet reached,while that of HM A-CAG-like group was 11.2 months,and the HM A-VEN group had a longer OS(P=0.055).There was no tumor lysis syndrome occurred in both groups.The main adverse reactions were digestive tract reaction,bone marrowsuppression and infection.The amount of agranulocytosis infection,pulmonary infection and platelet infusion in HM A-VEN group were significantly lower than those in HM A-CAG-like group(P<0.05),while the time of agranulocytosis and amount of erythrocyte infusion were similar(P>0.05).In HM A-Ven group 1 case died early,while in HM A-CAG-like group 8 cases died early due to pulmonary infection,respiratory failure,cerebral hemorrhage,and alveolar hemorrhage,the mortality in HM A-CAG-like group was significantly higher than that in HM A-VEN group(P=0.043).Among 43 patients,there was a significant difference in OS between HCT score 0-2 group and≥3 group(P=0.033).In HM A-CAG-like group,patients with HCT score≥3 had a worse prognosis(P=0.01),while in HM A-VEN group patients showed no statistically significant difference in prognosis(P=0.681).In HCT score 0-2 group,9 cases receiving HM A-VEN regimen and 22 cases receiving HM A-CAG-like regimen showed no statistical difference in OS(P=0.281).In HCT score≥3 group,7 cases receiving HM A-VEN regimen had a longer OS than 5 cases receiving HM A-CAG-like regimen(P=0.015).Conclusion:Venetoclax combined with HM A can achieve higher response rate,lower early mortality,and longer OS,especially in those with more comorbidities and poor tolerability.