Comparison Between Decitabine and Azacitidine for Patients With Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndrome: A Systematic Review and Network Meta-Analysis

Abstract

Background: The hypomethylating agents (HMAs) azacitidine (AZA) and decitabine (DAC) have been widely used in patients with acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (HR-MDS). However, few direct clinical trials have been carried out to compare the efficacy and adverse events (AEs) between these two agents. The clinical choice between them is controversial. A systematic review and network meta-analysis (NMA) was performed to compare the efficacy, safety, and survival of DAC and AZA in AML and HR-MDS patients.Methods: We systematically searched MEDLINE, Embase, Web of Science, and Cochrane Library through March 15, 2021. Randomized controlled trials (RCTs) on AML or HR-MDS patients comparing the efficacy and safety between DAC and AZA or comparing one of HMAs to conventional care regimens (CCR) were selected.Results: Eight RCTs (n = 2,184) were identified in the NMA. Four trials compared AZA to CCR, and four compared DAC to CCR. Direct comparisons indicated that, compared to CCR, both AZA and DAC were associated with higher overall response (OR) rate (AZA vs. CCR: relative risk (RR) = 1.48, 95% CI 1.05–2.1; DAC vs. CCR: RR = 2.14, 95% CI 1.21–3.79) and longer overall survival (OS) (AZA vs. CCR: HR = 0.64, 95% CI 0.50–0.82; DAC vs. CCR: HR = 0.84, 95% CI 0.72–0.98), and AZA showed higher rate of complete remission with incomplete blood count recovery (CRi) (HR = 2.52, 95% CI 1.27–5). For the indirect method, DAC showed a higher complete remission (CR) rate than AZA in patients with both AML (RR = 2.28, 95% CI 1.12–4.65) and MDS (RR = 7.57, 95% CI 1.26–45.54). Additionally, DAC significantly increased the risk of 3/4 grade anemia (RR = 1.61, 95% CI: 1.03–2.51), febrile neutropenia (RR = 4.03, 95% CI: 1.41–11.52), and leukopenia (RR = 3.43, 95% CI 1.64–7.16) compared with AZA. No statistical significance was found for the other studied outcomes.Conclusion: Compared to CCR, both AZA and DAC can promote outcomes in patients with AML and HR-MDS. DAC showed higher efficacy especially CR rate than AZA (low-certainty evidence), while AZA experienced lower frequent grade 3/4 cytopenia than patients receiving DAC treatment.

The emerging role of pyroptosis in pediatric cancers: from mechanism to therapy

“…Decitabine and azacitidine are classical drugs to treat myelodysplastic syndromes (MDS) or AML [ 171 , 172 ]. It is reported that these drugs can increase GSDME expression and sensitize the cancer cells to chemotherapy drug by inducing GSDME-mediated pyroptosis [ 62 , 63 ].…”

“…But gasdermin family proteins are still the potential biomarkers of tumor immunotherapy if we can upregulate gasdermin levels in tumor cells. Decitabine, a DNA methylation inhibitor drug which can upregulate GSDME expression in several cancers and increase their sensitivity to chemotherapy drug-induced pyroptosis, is undoubtedly a promising candidate [ 171 , 172 ]. Additionally, the exploration of small molecule drugs and the study of specific targeting carriers to target pyroptosis also shed good insights for pediatric cancer treatments.…”

Transcriptional and post-transcriptional regulation of checkpoint genes on the tumour side of the immunological synapse

“…4 and Rasmussen and Helin 2016 ). Not surprisingly, DNMT inhibitors, such as Azacitidine and Decitabine, appear to be promising antitumour chemotherapy drugs (Derissen et al 2013 ; Gu et al 2021 ; Ma and Ge 2021 ). However, considering that the resulting reduction in global DNA methylation might further promote tumour evasion of the immune response while reactivating tumour-suppressor genes, it might be beneficial to administer them alongside immune checkpoint inhibitors.…”

New Perspectives in Treating Acute Myeloid Leukemia: Driving towards a Patient-Tailored Strategy

“…In recent decades, the hypomethylating agents (HMAs) azacitidine and decitabine have become the preferred low-intensity options in AML treatment for unfit patients, allowing about one-third of treated patients to reach remission and transfusion independence, improving their overall survival (OS) and quality of life [ 3 , 4 , 5 ]. In particular, azacitidine has shown better outcomes compared to IC in poor cytogenetic risk patients and less myelotoxicity compared to decitabine [ 6 , 7 ].…”