Long term follow-up results of phase II clinical trial evaluating ruxolitinib (RUX) and azacitidine (AZA) combination therapy in patients (pts) with myelofibrosis (MF).

6572 Background: Monotherapy with JAK inhibitors improve spleen and symptom burden in MF, but their disease modifying effect is less clear. We conducted a phase 2 clinical trial evaluating the combination of RUX with hypomethylating agent AZA in MF. The interim analyses (Masarova et al.Blood, 2018) showed objective responses in 72% pts. We report the long-term follow-up of the full cohort of pts treated on this trial. Methods: The trial was conducted at MD Anderson Cancer Center, Houston including adult pts (≥ 18 years) with MF intermediate (Int) 1-2 or high-risk disease by Dynamic International Prognostic Scoring System (DIPSS). Responses were assessed per the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria. Results: From 3/2013-10/2021, 61 pts with a median age of 66 yrs (46-87) were treated (Table). Median Hb was 10.1 g/dl (6.8-16.2), and bone marrow blasts (BM) 2% (0-14%); 14 (23%) had BM blasts ≥ 5%. JAK 2 was mutated in 35 (57%); 38 pts (62%) had Int-2 or high risk DIPSS disease. IWG-MRT responses occurred in 44 pts (72%): clinical improvement (CI) in 37 (61%), including IWG-MRT CI spleen reduction >50% in 28/46 pts (61%) with baseline length ≥5 cm below left costal margin, and 31/51 pts (61%) with baseline TSS>12 having a >50% improvement in total symptom score (TSS 50). Partial response was seen in 4 pts and cytogenetic complete remission in 3 pts. With a median follow up of 93 mos, median overall survival (OS) was 46 mos (95% CI: 25-66), median event free survival was 33 mos (95% CI: 24-43) and median duration of any objective response was 43 mos (95% CI: 24-62). Transformation to AML occurred in 14 pts (23%) with median time to transformation of 19 mos (1-46). 20 pts (33%) received a stem cell transplant (SCT), 11 (55%) with Int-2/high risk DIPPS disease. Pts in the Int-2/high risk DIPPS group who got SCT had a trend towards improved median OS vs. those who did not (38 vs 27 mos, p=0.2). Grade ≥ 3 adverse events (AE) regardless of treatment attribution occurred in 30 pts (49%), most common were pneumonia (10,16%), anemia (7,12%), and sepsis (5, 8%). 3 pts had grade 5 AEs, and 4 pts were taken off study due to toxicity. Conclusions: 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. Clinical trial information: NCT01787487 . Table: see text