Maintenance therapy in AML: A meta-analysis and a single center retrospective study

Abstract Introduction Over the last decade, the overall survival of AML patients has improved due to steadfast progress in drug development, but it remains far from satisfactory. A considerable proportion of patients still relapse after achieving remission. Maintenance therapy is a potential strategy to improve prognosis and prolong remission durations for AML, but continues to be a subject of controversy. We conducted this meta-analysis and report the outcome of AML patients treated at our institution, aiming to evaluate the efficacy and safety of maintenance therapy in AML. METHOD A comprehensive literature search was conducted using both MeSH terms and free-text keywords, with the search limited to publications up to December 2024 and without language restrictions. Studies were screened based on predefined inclusion and exclusion criteria, followed by data extraction and quality assessment. Meta-analyses of outcomes including overall survival (OS), relapse-free survival (RFS), disease-free survival (DFS), and adverse events were performed using RevMan 5.3 and Stata 16.0 software. Based on the current research status of maintenance therapy for AML, this study conducted a meta-analysis and a retrospective analysis of clinical data from our center using the VA regimen to comprehensively evaluate the efficacy and safety of maintenance therapy in AML. Furthermore, a retrospective analysis was performed on unfit or elderly AML patients who received the VA regimen as maintenance therapy in the Second Department of Hematology at the Second Hospital of Hebei Medical University from August 2022 to December 2024. Patients were stratified by sex, age, pre-maintenance Minimal residual disease (MRD) status, and ELN risk classification. Survival curves were generated using the Kaplan-Meier method, and subgroup differences in OS and RFS were compared using the log-rank test. Results A total of 5178 patients from 9 studies were included, with follow-up durations ranging from 15.4 to 43.8 months. Therapeutic interventions were analyzed, including CC-486, sorafenib, gilteritinib, FLT3 inhibitors, azacitidine, and decitabine. Key findings show that the maintenance therapy group significantly prolonged OS [HR=0.49, 95% CI: 0.33-0.73, P=0.000] and RFS [HR=0.42, 95% CI: 0.27-0.66, P=0.000] compared to the control group. Subgroup analyses indicated that the benefits of maintenance therapy were most pronounced in patients with MRD+ (excluding post-transplant MRD+) and those with intermediate-risk cytogenetics (P<0.05). Common adverse events, such as neutropenia、thrombocytopenia、infection, and skin toxicity, were significantly higher in the maintenance therapy group, We retrospectively reviewed 24 unfit/elderly AML patients received VA maintenance therapy at our institution, The median age at diagnosis was 66 (27-77) years, 8 patients were MRD+ (25.00%) and 16 were MRD- (75.00%) Before maintenance therapy and 3 (12.50%) were in the low-risk group, 12 (50.00%) were in the intermediate-risk group, 9(37.50%) were in the high-risk group based on ELN stratification, With a median follow-up of 25.5 months (range: 5.9-46.4), the 2-year OS rate was 72.5% (95% CI: 45.5%-87.7%), and the 2-year RFS rate was 55.3% (95% CI: 32.6%-73.1%), Subgroup analysis showed no statistically significant differences in survival among the three risk groups stratified by the traditional ELN classification (P>0.05). However, patients with MRD- had significantly better OS and RFS compared to MRD+ patients (both P<0.05). The safety profile of the VA maintenance regimen was acceptable, with the most common adverse events being neutropenia, thrombocytopenia, and infections. Conclusions: The meta-analysis suggests that maintenance therapy in AML patientsis associated with improved OS, DFS, and RFS, with particularly pronounced benefits observed in MRD+ and intermediate-risk subgroups. Although maintenance therapy increases hematologic and dermatologic toxicities, its overall safety is acceptable. The retrospective analysis indicated that the VA regimen showed certain efficacy and safety in unfit or elderly AML patients, but the study is limited in number and needs more cases and a prospective cohort study to further verify.