The efficacy and adverse events of venetoclax in combination with hypomethylating agents treatment for patients with acute myeloid leukemia and myelodysplastic syndrome: a systematic review and meta-analysis

The use of allogeneic hematopoietic stem cell transplantation (HSCT) is recommended during the first complete remission of acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). However, only 30% of these cases have fully matched sibling donors (MSDs). Alternatively, matched unrelated donors (MUDs) and haploidentical (haplo) donors from first-degree relatives increase the access to transplantation, with some reported differences in outcomes. The current systematic review and meta-analysis was conducted with the aim of summarizing the results of those studies to compare the efficacy and toxicity of MSD-HSCT and MUD-HSCT versus haplo-HSCT for patients with AML or MDS. Articles published before September 15, 2018, were individually searched for in two databases (MEDLINE and EMBASE) by two investigators. The effect estimates and 95% confidence intervals (CIs) from each eligible study were combined using the Mantel–Haenszel method. A total of 14 studies met the eligibility criteria and were included in the meta-analysis. The overall survival rates were not significantly different between the groups, with pooled odds ratios of the chance of surviving at the end of the study when comparing haplo-HSCT to MSD-HSCT and comparing haplo-HSCT to MUD-HSCT of 0.85 (95% CI: 0.70 to 1.04; I 2 = 0%) and 1.12 (95% CI: 0.89 to 1.41; I 2 = 33%), respectively. The pooled analyses of other outcomes also showed comparable results, except for the higher grade 2 to 4 acute graft-versus-host disease (GvHD) for patients who received haplo-HSCT than those who received MSD-HSCT, and the better GvHD-free, relapse-free survival and the lower chronic GvHD than the patients in the MUD-HSCT group. These observations suggest that haplo-HSCT is a reasonable alternative with comparable efficacy if MSD-HSCT and MUD-HSCT cannot be performed. Nonetheless, the primary studies included in this meta-analysis were observational in nature, and randomized-controlled trials are still needed to confirm the efficacy of haplo-HSCT.

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Reduced-intensity versus Myeloablative Conditioning Regimens for Younger Adults with Acute Myeloid Leukemia and Myelodysplastic Syndrome: A systematic review and meta-analysis

Journal of Cancer ◽

10.7150/jca.46081 ◽

2020 ◽

Vol 11 (17) ◽

pp. 5223-5235

Author(s):

Shengling Ma ◽

Wei Shi ◽

Ziying Li ◽

Liang Tang ◽

Huafang Wang ◽

...

Keyword(s):

Systematic Review ◽

Acute Myeloid Leukemia ◽

Myelodysplastic Syndrome ◽

Myeloid Leukemia ◽

Meta Analysis ◽

Myeloablative Conditioning ◽

Younger Adults ◽

Conditioning Regimens ◽

Reduced Intensity ◽

Acute Myeloid

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

Frontiers in Pharmacology ◽

10.3389/fphar.2021.701690 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jiale Ma ◽

Zheng Ge

Keyword(s):

Systematic Review ◽

Acute Myeloid Leukemia ◽

Complete Remission ◽

Myelodysplastic Syndrome ◽

Myeloid Leukemia ◽

Meta Analysis ◽

Statistical Significance ◽

Cochrane Library ◽

Grade 3 ◽

Acute Myeloid

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.

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