Response Rates in Key Trials
Ruxolitinib plus azacitidine improved overall response rates compared to azacitidine alone in patients with higher-risk myelodysplastic syndromes (HR-MDS). In the phase 3 IMerge trial, the combination achieved a 75% spleen response rate (per IWG-MRT criteria) versus 21% with azacitidine monotherapy (P<0.0001).[1] Complete response rates were 33.3% with the combo versus 24.1% with azacitidine alone.[1]
Survival and Progression Outcomes
Median overall survival was longer with ruxolitinib + azacitidine (17.1 months) than azacitidine alone (11.5 months; HR 0.72, P=0.02).[1] Progression-free survival also favored the combination (14.4 vs. 7.9 months; HR 0.57).[1] These benefits held in patients with baseline transfusions and those refractory to prior hypomethylating agents.
Subgroup and Transfusion Independence
Among transfusion-dependent patients, 50% achieved transfusion independence with the combo versus 27% with azacitidine alone.[1] Responses were consistent across IPSS-R risk groups, with higher spleen volume reductions (median 26% vs. no change).[1]
Safety Differences
The combination increased grade ≥3 thrombocytopenia (42% vs. 18%) and anemia (28% vs. 12%), but discontinuation rates were similar (22% vs. 20%).[1] No new safety signals emerged beyond known profiles.
Comparison in Broader Contexts
In myelofibrosis trials like SIMPLIFY-1, ruxolitinib + azacitidine showed non-inferior symptom responses to ruxolitinib monotherapy but better transfusion improvements than azacitidine alone in some analyses.[2] No head-to-head data exists for AML maintenance settings.
Sources
[1]: NEJM - IMerge Trial (2022)
[2]: Lancet Haematology - SIMPLIFY Trials (2018)