OBJECTIVES: HR-MDS is associated with poor survival outcomes due to cytopenias and progression to acute myeloid leukemia (AML). This SLR aimed to identify clinical efficacy and safety evidence associated with HR-MDS treatments.

METHODS: MEDLINE, Embase, Cochrane Databases and the Database of Abstracts of Reviews of Effects were searched in October 2022, supplemented by hand-searches of grey literature and SLR bibliographies. Eligible articles reported interventional or observational studies of pharmacological management of HR-MDS. Study quality was assessed using the ROBINS-I and University of York's Centre for Reviews and Dissemination checklists.

RESULTS: Of 8,821 records retrieved, 59 unique studies were included. Most assessed hypomethylating agents (HMA) monotherapies (n=34, 23 assessing azacitidine), and HMA+venetoclax (n=10, 5 assessing azacitidine+venetoclax). Median overall survival (OS) (n=17) ranged from 7.3 (best supportive care [BSC], which includes antibiotics, erythropoietin treatment, and transfusions) to 28.2 months (azacitidine+venetoclax). The only statistical improvement in median OS between treatments was azacitidine compared with BSC (16.9 versus 7.3 months, p=0.039, n=1). Median progression-free survival (n=4) ranged from 1.05 (azacitidine) to 17.5 months (azacitidine+venetoclax). Objective response rate (n=23) ranged from 0% (BSC) to 93.3% (decitabine+low-dose cytarabine). Median time to AML progression (n=5) ranged from 2 (BSC) to 19.3 months (HMA), with decitabine significantly delaying time to progression compared with BSC (p=0.03). 33.3–50% of patients became transfusion independent following azacitidine treatment, compared with 25–46.5% following azacitidine+venetoclax and 58% following magrolimab+azacitidine (n=5). 0% (intensive chemotherapy and sabatolimab+HMA) to 14.4% (azacitidine) of patients discontinued treatment due to adverse events (n=5).

CONCLUSIONS: Clinical and safety outcomes for patients are poor and there remains an unmet medical need. HMA monotherapy and combination therapies were associated with better outcomes compared with BSC and chemotherapy, with combinations demonstrating the greatest benefit. A quantitative treatment comparison would be valuable to capture the absolute and relative benefits of HR-MDS treatments.