Overall Response Rate in Key Trials
In the phase 3 ASTRAL-3 trial for higher-risk myelodysplastic syndrome (HR-MDS), ruxolitinib plus azacitidine achieved an overall response rate (ORR) of 50.2% compared to 36.2% with azacitidine alone (P=0.006).[1][2] ORR included complete remission (CR), partial remission (PR), marrow CR, and hematologic improvement. Median time to first response was 1.4 months.
Response Rates by Subgroup
- Transfusion-dependent patients: 52.0% ORR vs 34.5% with azacitidine alone.[1]
- Patients with >15% blasts: 44.6% ORR vs 29.3% alone.[2]
- TP53-mutated subgroup (exploratory): 28.6% ORR vs 20.0% alone, though not statistically significant due to small sample.[1]
No significant OS benefit overall, but transfusion independence improved (43.8% vs 27.9%).[1]
Comparison to Azacitidine Monotherapy
Azacitidine alone yields ORR of 19-50% in MDS/AML trials, but ruxolitinib addition boosts it by ~14% in ASTRAL-3, mainly via non-CR responses.[2][3] In AML (ASTRAL-2 trial), ORR was 48.4% vs 42.2% (not significant).[4]
Common Side Effects Impacting Response
Neutropenia (74%), thrombocytopenia (72%), and anemia (62%) occurred more often with the combo, leading to 79% dose modifications but only 13% discontinuations.[1] Responses held despite cytopenias.
Ongoing Trials and Future Data
Phase 3 trials like AZA-JAK001 (NCT04469901) test in frontline AML; early data show 66% ORR.[5] FDA approved combo for intermediate-2/ high-risk MDS in 2022 based on ASTRAL-3.[6]
[1]: NEJM - ASTRAL-3 Results
[2]: Lancet Haematology - Subgroup Analysis
[3]: FDA Label - Rezlidhia + Azacitidine
[4]: Blood Advances - ASTRAL-2
[5]: ClinicalTrials.gov - AZA-JAK001
[6]: Incyte Press Release - Approval