AML-294: Maintenance Therapy After Allogeneic Hematopoietic Transplant for Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis

Abstract

Context: Allogeneic hematopoietic stem cell transplant (HSCT) is a standard therapy for patients with acute myeloid leukemia (AML), when the risk for relapse overweighs projected transplant-related morbidity and mortality. Disease relapse remains the most common reason for transplant failure and patient death, and treatment of relapse remains extremely challenging. Reducing the risk of post-transplant relapse without unwanted toxicity by means of post-transplant maintenance therapy has recently been studied in several prospective studies. Objectives: We aimed to evaluate the efficacy and safety of maintenance therapy for AML after allogeneic HSCT. Design, Setting and Patients: Systematic review and meta-analysis of randomized controlled trials which compared maintenance therapy with observation or placebo in AML patients after allogeneic HSCT. The Cochrane Library, PubMed, conference proceedings, and references were searched until February 2021. Primary outcome was overall survival (OS). Secondary outcomes included relapse free survival (RFS), relapse rate, and safety (including adverse events and GVHD). Results: Our search yielded five trials conducted between the years 2009 and 2018, including 736 patients, all published in peer-reviewed journals. Maintenance therapy comprised of tyrosine kinase inhibitors (TKI) – i.e., sorafenib - 2 studies and midostaurin - 1 study as well as hypomethylating agents (HMAs), namely decitabine and azacytidine - one study each. Maintenance after allogeneic HSCT was associated with an improved OS, HR=0.61 (95% CI 0.47-0.80). Subgroup analyses by type of maintenance therapy revealed advantage in OS with either TKI or HMA maintenance [HR=0.50 (95% CI 0.33-0.77) and HR=0.69 (95% CI 0.49-0.98), respectively]. Data from five trials was available for RFS analysis and showed improved RFS in the maintenance group compared to the control arm HR=0.51 [95% CI 0.40 - 0.66]. Relapse rate was significantly decreased in the maintenance arm compared to the control arm, RR=0.41 (95% CI 0.20-0.88, 4 trials). Regarding safety, there was no difference between the arms concerning adverse events (AE), including grade 3-4 AE, rate of infections and acute and chronic GVHD. Conclusions: Our meta-analysis shows that post-transplant maintenance therapy in AML patients is effective in decreasing relapse rate and improving RFS and OS, with a satisfactory safety profile.