Efficacy And Safety Of Hypomethylating Agents Combined With BCL-2 Inhibitor Or Half-Dose Priming Regimen In The Treatment Of Acute Myeloid Leukemia Intolerant To Intensive Chemotherapy

Objective: To investigate the efficacy and safety of hypomethylating agents combined with BCL-2 inhibitor or half-dose priming regimen in the treatment of acute myeloid leukemia intolerant to intensive chemotherapy.Methods: The medical records of 102 patients with AML who were intolerant to intense chemotherapy were analyzed retrospectively.Among them,42 patients were treated with HMAs combined with BCL-2 inhibitor,and 60 patients were treated with HMAs combined with half-dose priming regimen.The clinical data and clinical outcome of patients were collected by medical HIS system and telephone.The main end points were complete remission rate(CR),complete remission with incomplete hematologic recovery(CRi)and overall survival(OS).Secondary end points were total remission rate(ORR),event-free survival(EFS)and hematological and non-hematological adverse reactions.Statistical software SPSS25.0 was used to analyze the data.If the measurement data conforms to the normal distribution,T-test was used;if it does not conform to the normal distribution,nonparametric test was used.Chi-square test and Fisher exact probability method were used for counting data.Multivariate analysis of efficacy was performed by binary logistic regression analysis.OS and EFS were evaluated using Kaplan-Meier method,and differences between groups were compared by log-rank test.Multivariate analysis of prognosis was performed using Cox proportional risk model.p< 0.05 indicated statistically significant difference.Results: There was no significant difference in baseline characteristics between the two groups(p >0.05).After a cycle of treatment,6.9% of the newly treated patients reached CR.CR in BCL-2 inhibitor group was 19%,and only 2% patients in half-dose priming regimen group reached CR,which was statistically different(p =0.023).The CR/CRi of all newly treated patients was 44.1%,and the CR/CRi of BCL-2 inhibitor group was better than that of half-dose priming regimen group(85.7% vs 31.4% p < 0.001).The ORR of the newly treated patients was 70.8%,and the ORR of the BCL-2 inhibitor group was better than that of the half-dose priming regimen group(95.2%vs60.8% p =0.004).In patients with refractory recurrence,the remission rate of BCL-2 inhibitor group was higher than that of half-dose priming regimen group,but the difference was not statistically significant(p> 0.05).The median OS of the newly treated patients in the BCL-2 inhibitor group was 11.13 months,and that in the half-dose priming regimen group was 7.57 months,with a statistical difference between them(p =0.030).The median EFS of the newly treated patients in the BCL-2 inhibitor group was10.63 months,and that in the half-dose priming regimen group was3.6months.There was a statistical difference between them(p =0.001).The median OS of relapsed and refractory patients was 9.8 months in BCL-2inhibitor group and 4.07 months in half-dose priming regimen group,and there was no statistical difference between them(p =0.053).The median EFS of relapsed and refractory patients was 9.8months in the BCL-2inhibitor group and 2.6 months in the half-dose priming regimen group,with a statistical difference between them(p =0.034).After the first cycle of treatment,there was a significant difference in platelet reduction between the half-dose priming regimen group and the BCL-2 inhibitor group(p <0.001),and the half-dose priming regimen group had an effect on platelet reduction.There was no significant difference in non-hematological adverse reactions between the two groups(p > 0.05).Conclusion: The induced remission rate of HMAs combined with BCL-2inhibitor in the treatment of newly treated patients with acute myeloid leukemia who are intolerant to intense chemotherapy is better than that of HMAs combined with half-dose priming regimen.It can prolong the survival time of newly treated patients who are intolerant to intense chemotherapy,and can prolong the event-free survival of relapsed and refractory patients who are intolerant to intense chemotherapy.No increase in adverse reactions was observed,and the safety was good.