A systematic review of higher-risk myelodysplastic syndromes clinical trials to determine the benchmark of azacitidine and explore alternative endpoints for overall survival

The hypomethylating agent azacitidine can prolong overall survival (OS) in patients with higher risk-myelodysplastic syndromes (HR-MDS) compared to conventional regimens. However, outcomes differ largely between studies, making it challenging determine the contribution of novel therapies added azacitidine. Further, a discrepancy is seen complete (CR) or partial (PR) response rates and OS improvement azacitidine, rely on earlier endpoints than OS. We conducted systematic literature search study-level review 237 clinical studies better understand for HR-MDS treated Pooled marrow CR was 9% (N = 2654; 95% CI: 6–13 %), rate 17 % 6943; 15–20 median (mOS) 18.6 months 2820; 15.3–21.9). A weak correlation mOS detected (207 patient cohorts, Pearson’s r 0.315; P < 0.0005), much stronger progression-free (mPFS) (r=0.88, 3 × 10?14). Six-months correlated 1-year but were only infrequently reported 41 cohorts) therefore not allowing robust recommendation surrogate established endpoint. Larger numbers patient-level data appear necessary, especially designing future trials using combinations.