Azacitidine in combination with ruxolitinib demonstrates promising efficacy for patients with myelofibrosis (MF), according to long-term follow-up results from a phase 2 clinical trial presented at the 2024 American Society of Clinical Oncology (ASCO) Annual meeting.

The trial included adult patients aged ≥18 years with MF intermediate 1 to 2 or high-risk disease, measured by the Dynamic International Prognostic Scoring System (DIPSS). From March 2013 to October 2021, a total of 61 patients were treated in the trial. Patients had a median age of 66 years (46 to 87). The median hemoglobin was 10.1 g/dl (6.8 to 16.2) and bone marrow blasts 2% (0 to 14%). Overall, 14 (23%) patients had BM blasts ≥5%. Furthermore, JAK2 was mutated in 35 (57%) patients and 38 (62%) patients had intermediate-2 or high-risk DIPSS disease.

Study results showed an International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) response occurred in 44 (72%) patients. A clinical improvement was noted in 37 (61%) patients, including IWG-MRT spleen reduction >50% in 28 (61%) of 46 patients with baseline length ≥5 cm below left costal margin, and 31 (61%) of 51 patients with baseline total symptom score (TSS) >12 having a >50% improvement in TSS 50. In addition, a partial response was seen in 4 patients and cytogenetic complete remission in 3 patients.

With a median follow-up of 93 months, median overall survival (OS) was 46 months (95% confidence interval [CI], 25 to 66), median event-free survival was 33 months (95% CI, 24 to 43), and median duration of any objective response was 43 months (95% CI, 24 to 62). It was noted that disease transformation to AML occurred in 14 (23%) patients with a median time to transformation of 19 months. In addition, 20 (33%) patients received a stem cell transplant (SCT), and 11 (55%) patients had intermediate-2/high-risk DIPPS disease. It was observed that patients in the Intermediate-2/high-risk DIPPS group who received a SCT showed a trend towards improved median OS vs those who did not receive a transplant (38 vs 27 months, P = .2).

Safety data showed that grade ≥3 adverse events (AEs), regardless of treatment attribution, occurred in 30 (49%) patients. The most common AEs were pneumonia (10; 16%), anemia (7; 12%), and sepsis (5; 8%). It was noted that 3 patients had grade 5 AEs, and 4 patients were taken off study due to toxicity.

“Long term follow-up data from this phase 2 clinical trial shows good efficacy of the AZA-RUX combination in MF, with durable responses and promising survival outcomes,” concluded first author Sankalp Arora, MD, The University of Texas MD Anderson Cancer Center, Houston, Texas and colleagues.

Source:

Arora S, Senapati J, Masarova L, et al. Long term follow-up results of phase II clinical trial evaluating ruxolitinib (RUX) and azacitidine (AZA) combination therapy in patients (pts) with myelofibrosis (MF). Presented at the ASCO Annual Meeting. May 31–June 4, 2024; Chicago, IL. Abstract 6572