In September 2023, a study led by professor Erlie Jiang from Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science published in Hematological Oncology, focused on the effectiveness of azacytidine (AZA) maintenance therapy post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML). Through propensity score matching, the research compared 78 treated patients with 102 historical controls, revealing that AZA significantly improves relapse-free survival without severe adverse effects. This study, by demonstrating the potential of AZA maintenance to reduce relapse in AML patients, marks a significant contribution to the field of hematological oncology and opens new avenues for personalized post-transplant care.
The management of acute myeloid leukemia (AML) remains a significant clinical challenge, particularly for patients who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The risk of relapse remains a primary concern, with recurrence rates contributing to substantial mortality. In this context, maintenance therapies that can prevent relapse and extend survival are critically needed. Azacytidine (AZA), a hypomethylating agent, has emerged as a potential candidate for maintenance therapy. This study evaluates the efficacy and safety of AZA as a maintenance therapy in reducing relapse rates among patients with AML, focusing on those at high risk of recurrence post-allo-HSCT.
This prospective, one-arm study targeted a specific patient cohort: individuals diagnosed with myeloid malignancy exhibiting high relapse risk after receiving allo-HSCT. Seventy-eight patients were enrolled between September 2019 and April 2022, based on inclusion criteria emphasizing recent transplantation and a high risk of recurrence. For comparative analysis, 102 matched historical controls were identified through propensity score matching to account for baseline characteristics and potential confounders. AZA was administered at a dosage of 50 mg/m^2, either subcutaneously or intravenously, over five days starting on day +60 post-transplantation, repeated every 28 days. Monitoring and assessment included regular follow-ups for adverse events, relapse rates, and overall survival, with the primary endpoint being relapse-free survival (RFS).
With a median follow-up of 19.6 months, the study found that AZA maintenance therapy significantly improved RFS (log-rank test, p = 0.01) compared to the historical control group. Specifically, the 1-year RFS was 87.7% in the AZA group versus 72.2% in the control group. The hazard ratio for relapse or death was significantly lower in the AZA group (HR=0.21, 95% CI, 0.09–0.47; p<0.01), indicating a robust protective effect against relapse. Notably, the benefits of AZA therapy were more pronounced in refractory AML patients categorized under favorable or intermediate risk according to the European Leukemia Net guidelines. The interaction between risk category and treatment effect was statistically significant (p for interaction=0.03), highlighting the importance of patient selection in optimizing maintenance therapy outcomes.
The study’s Kaplan-Meier analyses indicated that azacytidine (AZA) maintenance therapy significantly improved relapse-free survival (RFS) and overall survival (OS) compared to controls, with particular benefit seen in patients with favorable/intermediate-risk AML according to the European Leukemia Net (ELN) guidelines. Multivariable analysis revealed AZA’s hazard ratio for RFS at 0.21, highlighting its effectiveness after adjusting for various factors. Chronic graft-versus-host disease (cGVHD) emerged as a protective factor for both OS and RFS, while lack of remission before hematopoietic cell transplantation (HCT) was a significant risk factor, demonstrating the complex interplay of disease status and transplant outcomes.
In this study, azacytidine (AZA) maintenance therapy post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) showed a notable improvement in relapse-free survival (RFS) without increasing adverse events significantly, despite a higher dose of 50 mg/m^2. Myelosuppression was the primary side effect, with no grade 4 adverse effects or therapy-related deaths reported. Subgroup analysis highlighted the therapy’s benefit especially in patients with acute myeloid leukemia (AML), women, female donors to male recipients, younger patients and donors, and those within the favorable/intermediate-risk categories. These findings contrast with a phase III trial by Oran that found no significant difference in RFS or overall survival with a lower AZA dose, underscoring the potential of a 50 mg/m^2 dose for better outcomes and safety.
The findings from this study underscore the potential of AZA maintenance therapy as a significant advancement in the post-transplant management of AML. By substantially reducing the risk of relapse, AZA offers hope for improved outcomes in a high-risk patient population. Importantly, the differential benefit observed among patients with favorable or intermediate-risk AML suggests that patient stratification could further enhance the efficacy of maintenance therapies. As safety profiles were acceptable and manageable, AZA represents a viable option for extending remission and improving survival.
The positive outcomes associated with AZA maintenance therapy signal a promising direction for future research and clinical practice. By preventing relapse and extending survival in patients with myeloid malignancy post-allo-HSCT, AZA has the potential to redefine maintenance therapy standards. However, the need for further research remains, particularly in identifying patient subgroups most likely to benefit and in exploring the long-term implications of such therapy. As the understanding of AML biology and post-transplant care continues to evolve, therapies like AZA will play a crucial role in improving patient outcomes.
