Safety and infection risk factors in elderly acute myeloid leukemia patients undergoing induction therapy with venetoclax combined with hypomethylating agents

老年急性髓系白血病患者接受维奈托克联合去甲基化药物诱导治疗的安全性和感染风险因素

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Abstract

OBJECTIVE: To retrospectively analyze the incidence of infections in elderly acute myeloid leukemia (AML) patients undergoing induction therapy with venetoclax combined with hypomethylating agents and to compare these findings with those from patients receiving standard or low-dose chemotherapy. METHODS: Medical records of 169 elderly (≥60 years old) AML patients diagnosed via MICM (morphology, immunology, cytogenetics, and molecular genetics) at the First Affiliated Hospital of USTC between June 2019 and June 2022 were reviewed. Patients were divided into three groups: venetoclax combined with hypomethylating agents group (targeted therapy group), standard chemotherapy group, and low-dose chemotherapy group. Comparisons were made across groups regarding bacterial infection rates, fungal infection cases, infection sites, and severity. RESULTS: The median ages at diagnosis in the targeted therapy group, standard chemotherapy group, and low-dose chemotherapy group were 73, 68, and 71 years, respectively (P<0.05). Compared with the standard chemotherapy and low-dose chemotherapy groups, the targeted therapy group had a higher prevalence of comorbidities (P<0.05). Complete remission rates in targeted therapy group, standard chemotherapy group, and low-dose chemotherapy group were 68.8%, 51.2%, and 26.4%, respectively (P<0.05). The durations of neutropenia were 9.0±8.4, 15.0±15.0, and 9.3±9.1 days, respectively (P<0.05). Bacterial infection rates were 87.5%, 95.2%, and 94.3% (P<0.05), with the most common sites being the lungs, bloodstream, upper respiratory tract, and unspecified sites. The durations of fever were 2.34±3.59, 4.52±4.38, and 3.53±4.76 days, respectively (P<0.05). The proportions of patients receiving antifungal prophylaxis were 46.8%, 46.4%, and 41.5%, respectively (P>0.05), mainly involving voriconazole and posaconazole. The proportions of clinically diagnosed or confirmed fungal infections were 6.3%, 9.5%, and 9.4%, respectively (P>0.05). The proportions of patients requiring initiation of antifungal therapy were 34.4%, 48.8%, and 43.4%, respectively (P<0.05). Among the 169 elderly AML patients, three (1.8%) developed infection-induced multiple organ dysfunction syndrome (i-MODSE), all in the standard chemotherapy group. CONCLUSION: Venetoclax combined with hypomethylating agents shows a favorable safety profile and reduced infection risk in the treatment of AML in the elderly patients. Meanwhile, nontargeted therapies, a prolonged duration of neutropenia, and a prolonged duration of fever were found to be independent risk factors for fungal infections and the need for antifungal intervention.

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