A recent study indicates that a combination of decitabine and the CHAG (cytarabine, aclarubicin, homoharringtonine, and G-CSF) priming regimen demonstrates significant efficacy and a favorable safety profile in patients with relapsed/refractory acute myeloid leukemia (R/R AML). The findings suggest a potential new approach for treating this challenging patient population.
The study, a single-center retrospective analysis, involved 62 patients with R/R AML. Results showed that 46 patients achieved complete remission (CR), representing 74.2%, while 5 patients experienced partial remission (PR), resulting in an overall response rate (ORR) of 82.2%. These outcomes are particularly noteworthy given the poor prognosis typically associated with R/R AML, where conventional treatments often yield limited success.
Current Treatment Landscape and the Role of Decitabine
AML prevalence increases with age, and R/R AML presents a significant therapeutic challenge. While targeted therapies have improved AML treatment, a standard option for R/R AML remains elusive. Traditional regimens like high-dose Ara-C and FLAG have remission rates of 30-45% but come with high chemotherapy-related mortality and a low 2-year overall survival (OS) rate of only 10%. The MEC regimen shows an ORR of 43.7% and an OS of 5.3 months in R/R AML patients.
Decitabine, a DNA methyltransferase inhibitor, has shown promise in treating hematological malignancies by promoting DNA demethylation and activating tumor suppressor genes. Prior studies indicate that single-agent decitabine achieves a CR rate of approximately 20% in relapsed elderly AML patients. Combining decitabine with other anti-tumor drugs, such as Ara-C and CAG regimens, has yielded improved efficacy.
The CHAG Priming Regimen and Study Outcomes
The CHAG priming regimen, which includes homoharringtonine (HHT), a plant-derived antitumor drug, has previously demonstrated efficacy in R/R AML patients. The current study builds upon these findings by combining decitabine with CHAG. Of the 46 patients who achieved CR, 34 were MRD-negative, indicating deeper remissions compared to the CHAG regimen alone.
Survival analysis revealed a median relapse-free survival (RFS) of 4.3 months (0.3–65 months) and a median overall survival (OS) of 7.75 months (1–66.3 months) in the 62 patients. While early allo-HSCT after CR has been shown to prolong survival, this study found no significant difference in OS between patients who continued chemotherapy after CR and those who underwent bridging allo-HSCT, possibly due to the small number of patients undergoing transplantation.
Safety and Tolerability
The most common adverse reaction associated with the decitabine-CHAG combination was myelosuppression. Non-hematologic adverse reactions included infection, gastrointestinal issues, fever, and oral mucositis. Importantly, no serious cardiac, hepatic, or renal impairment was observed, and there were no treatment-related deaths, highlighting the regimen's tolerability.
Limitations and Future Directions
The study acknowledges limitations, including its single-center, retrospective design, limited sample size, and short observation period. The researchers emphasize the need for larger, multi-center studies with longer follow-up periods to validate these findings and further explore the potential of decitabine combined with the CHAG priming regimen in treating R/R AML.
