Objective This study aimed to evaluate the efficacy and safety of venetoclax(VEN)combined with hypomethylating agents(HMA)in the treatment of higher-risk myelodysplastic syndromes(HR-MDS)and analyze the factors influencing their therapeutic effect.Methods The clinical data of 83 patients with HR-MDS who were diagnosed at the First Affiliated Hospital of Zhengzhou University between November 2019 and May 2023 were retrospectively analyzed.All patients were treated with VEN combined with HMA.The Kaplan-Meier method was used to depict the survival curves,and the log-rank test was used to compare survival between the groups.Results The median age was 57(15-82)years old,and 51 patients(61.4％)were male.Forty-five patients(54.2％)were initially treated with HMA,23(27.7％)received ≤4 cycles of HMA,and 15(18.1％)demonstrated HMA failure.At the median follow-up of 10.3(0.6-34.4)months,the overall response rate(ORR)was 62.7％(52/83),including 18 patients(21.7％)with a complete response(CR),14(16.9％)with a bone marrow CR(mCR)with hematological improvement,and 20(24.1％)with a mCR.The ORR of patients with initial treatment,≤4 HMA cycles,and HMA failure were 66.7％,60.9％,and 53.3％,respectively(P=0.641).The median overall survival time was 14.6(95％CI 7.2-22.0)months,and the median progression-free survival time was 8.9(95％CI 6.7-11.1)months.The multivariate analysis showed that serum alkaline phosphatase(ALP)≥90 U/L(OR=14.574,95％CI 3.036-69.951,P=0.001),TP53 mutation(OR=13.052,95％CI 1.982-85.932,P=0.008),and U2AF1 mutation(OR=7.720,95％CI 1.540-38.698,P=0.013)were independent risk factors for poor efficacy of VEN combined with HMA.Hematological toxicity occurred in all patients,and the incidence of treatment-induced grade 3-4 leukopenia was 48.2％(40/83).Infection was the most common non-hematological adverse event,mainly pulmonary infection(31.3％).Conclusion VEN combined with HMA had a high response rate in patients with HR-MDS,both at initial treatment and with HMA failure.ALP ≥ 90 U/L,TP53 mutation,and U2AF1 mutation were independent risk factors for non-response to treatment.
NETL
NSTL
维普
万方数据
