Analysis Of The Efficacy And Safety Of Venetociax Combined With Hypomethylating Agents In Patients With Acute Myeloid Leukemia

Objective:To investigate the efficacy and safety of venetoclax combined with hypomethylating agents in untreated acute myeloid leukemia(AML)patients who are ineligible for intensive therapy(unfit)and relapsed/refractory acute myeloid leukemia patients,and to analyze the factors that may affect the efficacy and survival,providing more clinical evidence for patients with acute myeloid leukemia.Methods:A retrospective analysis was made of 87 patients with acute myeloid leukemia treated with venetoclax combined with hypomethylating agents in Qilu Hospital of Shandong University from July 2020 to October 2022,all of whom were untreated unfit AML patients or relapsed/refractory AML patients.The clinical data of the patients were collected and the clinical characteristics were summarized and analyzed,the efficacy and survival of venetoclax combined with hypomethylating agents were evaluated,and the factors that might affect the efficacy and survival were analyzed;The adverse reactions and tolerance of patients during treatment were followed up.Results:1.Baseline characteristics:A total of 87 AML patients treated with venetoclax combined with hypomethylating agents were included in this study,including 49 patients with untreated unfit AML and 38 patients with relapsed/refractory AML(27 patients with relapsed AML and 11 patients with refractory AML).The median age of patients was 62 years old,with 35 males(40.23%)and 52 females(59.77%).There were 77 cases of primary AML(88.51%)and 10 cases of secondary AML(11.49%);the most common FAB classification was M5,with a total of 53 cases(60.92%).The median peripheral white blood cell count before treatment was 4.41*109/L and the median bone marrow blast count was 51.50%.Prognostic risk stratification was performed according to the 2022 edition of the European Leukemia Network(ELN)expert recommendations for the diagnosis and management of AML in adults:17 cases(19.54%)in the favorable group,35 cases(40.23%)in the intermediate group,and 35 cases(40.23%)in the adverse group.The patients with FLT3,NPM1 and IDH mutations were 23(26.44%),24(27.59%)and 25(28.74%)respectively.2.Efficacy evaluation:(1)The median treatment course was 3 in the untreated unfit AML group.After one course of treatment,21 patients(42.86%)achieved CR,38 patients(77.55%)achieved cCR,ORR was 83.67%(41/46),and 17 patients’(34.69%)MRD turned negative.(2)The median treatment course was 2 in the relapsed/refractory AML group.After one course of treatment,9 patients(23.68%)achieved CR,20 patients(52.63%)achieved cCR,ORR was 60.53%(23/38),and 13 patients’(31.58%)MRD turned negative.(3)The univariate analysis of the efficacy of the untreated unfit group showed that the type of AML had a statistically significant difference in the cCR rate after one cycle(P=0.029);Age(P=0.046)and AML type(P=0.006)had statistical significance on ORR after one cycle;IDH mutation had a statistically significant difference in ORR after one cycle(P=0.043).Multivariate analysis showed that age ≥65(P=0.043)and secondary AML(P=0.009)were independent risk factors affecting ORR after one cycle.(4)The univariate analysis of the efficacy in the relapsed/refractory group showed that the IDH mutation had a statistically significant difference in the cCR rate(P=0.038)and the MRD negative conversion rate(P=0.007)after one cycle.Multivariate analysis showed that IDH mutation was an independent favorable factor for cCR(P=0.020)and negative MRD(P=0.005)after one cycle.3.Survival analysis:(1)In the untreated unfit group,the median follow-up time was 14 months,the median survival time was not reached,and the 1-year cumulative survival rate was 64.6%.In the relapsed/refractory group,the median follow-up time was 8 months,the median survival time was 9 months(95%confidence interval:1.063-16.937),and the one-year cumulative survival rate was 46.7%.(2)The univariate analysis of the effect of NPM1 mutation on overall survival in the untreated unfit group showed a statistically significant effect(P=0.049).No independent factors were identified by COX multivariate regression analysis for overall survival.(3)The univariate analysis of the effect of negative MRD after one cycle on overall survival in the relapsed/refractory group showed a statistically significant effect(P=0.008).COX multivariate analysis suggested that negative MRD after one cycle was an independent favorable factor for survival(P=0.035).4.Safety evaluation:The incidence of hematological adverse reactions was 100.00%(87/87),and the most common adverse reaction was leukopenia(87/87,100.00%).The most common non-hematological adverse reaction was infection(76/87,87.36%);tumor lysis syndrome occurred in one patient in the untreated unfit group and one patient in the relapsed/refractory group.Conclusion:1.Venetoclax combined with hypomethylating agents can achieve high treatment response rates and long survival time in both untreated unfit AML and relapsed/refractory AML patients.2.Untreated unfit AML patients younger than 65 years old,primary untreated unfit AML patients and IDH-mutated relapsed/refractory AML patients may show higher treatment response rate.Patients with relapsed/refractory AML who achieved MRD negative after one cycle may have longer survival.3.Almost all patients treated with venetoclax combined with hypomethylating agents will experience adverse reactions,especially hematological adverse reactions,but most patients can tolerate them after the addition of corresponding symptomatic treatment,serious adverse reactions are rare.During the treatment,it is necessary to strengthen the monitoring of tumor lysis syndrome and timely symptomatic treatment.