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Final analysis of phase 2 clinical trial of ruxolitinib and azacitidine combination therapy in patients with myelodysplastic syndrome/myeloproliferative neoplasms

By: Arora, Sankalp, Senapati, Jayastu, Deshmukh, Indraneel, Bose, Prithviraj, Masarova, Lucia, Loghavi, Sanam, Wang, Xuemei, Nogueras-Gonzalez, Graciela, Montalban-Bravo, Guillermo, Borthakur, Gautam, DiNardo, Courtney D., Kadia, Tapan, Zhou, Lingsha, Saenz, Dyana, Halim, Habiba, Alvarado, Yesid, Ohanian, Maro, Takahashi, Koichi, Short, Nicholas J., Jabbour, Elias, Ravandi, Farhad, Garcia-Manero, Guillermo, Pemmaraju, Naveen, Daver, Naval G.

BioMed Central
2026-06-16; doi: 10.1186/s13045-026-01813-7

Abstract

Background

Myelodysplastic syndrome and myeloproliferative neoplasm (MDS/MPN) overlap syndromes are characterized by the presence of features of both MDS and MPN and have a poor prognosis. We conducted a phase 2 clinical trial evaluating the combination of Azacitidine (AZA) and Ruxolitinib (RUX) in MDS/MPN, with interim analysis showing an objective response rate of 57%. Herein, we report the final analysis from this clinical trial, including long-term survival data.

Methods

This was an open-label phase 2 clinical trial including adult patients in 2 diagnostic arms: myelofibrosis (arm 1) and MDS/MPN (arm 2). This manuscript reports outcomes of MDS/MPN patients. RUX 5–20 mg twice daily (per RUX label) was administered in 28-day cycles, and AZA 25 mg/m² on days 1–5 was added starting cycle 4. Primary endpoint was objective response rate per the 2015 International Consortium Proposal (ICP) MDS/MPN response criteria.

Results

From 5/2013 to 8/2022, 52 patients were treated with a median age of 68 years (range, 39–82). Disease subtypes were MDS/MPN-Unclassifiable in 24 patients (46%), chronic myelomonocytic leukemia in 23 patients (44%), and atypical chronic myeloid leukemia in 5 patients (10%). Majority of patients (n = 40, 77%) had intermediate-2/high-risk disease by Dynamic International Prognosis Scoring System criteria. Objective responses were attained in 30 patients (58%), with a median duration of response of 13.6 months (95% CI: 6.4–41.1). After a median follow up of 88.5 months, 13 (25%) patients are alive, with median overall survival (OS) of 26.7 months (95% CI: 16.5–52.7), 5-year OS 33%. Median OS in MDS/MPN-U and CMML was 52.7 months (5-year OS 46%) and 17.5 months (5-year OS 27%), respectively. Twelve patients (23%) underwent allogeneic stem cell transplantation; with median OS not reached, 5-year OS 51%. Transformation to acute myeloid leukemia occurred in 13 patients (25%). The most common grade 3–5 adverse events (AEs) regardless of attribution were anemia (31, 60%), thrombocytopenia (27, 52%) and pneumonia (17, 33%). AE-related treatment discontinuation occurred in only 3 patients (6%).

Conclusions

AZA-RUX therapy led to durable responses and encouraging OS in MDS/MPN with a manageable safety profile.

Trial registration

NCT01787487, (clinicaltrials.gov, date: 2/6/2013)