P207 | HIGH-ALLELE BURDEN JAK2 MUTATION IN LOW-RISK PV: AN ADDITIONAL RECOMMENDATION TO START “EARLY” CYTOREDUCTION? RESULTS FROM A MULTICENTRIC STUDY

Background. Polycythemia vera (PV) is a MPN characterized by high red blood cell mass and thrombotic risk. Cytoreduction is offered to high-risk patients (pts) due to age or thrombosis history/occurrence, to prevent further ones. Recommendations suggest early cytoreduction (EC) in low-risk (LR) PV for phlebotomy intolerance, progressive cytosis, splenomegaly or symptoms. To date, high JAK2 variant allele frequency (VAF) does not guide treatment, though being associated with venous thrombosis. We therefore explored JAK2 VAF role regarding EC and thrombosis in LR PV. Methods. We retrospectively included 75 WHO-defined LR PV pts diagnosed at the Hematology Divisions of Udine, Trieste and Graz from 2009 to 2024, with JAK2 VAF available at diagnosis or before cytoreduction. A 50% cut-off was set to distinguish high (HB) from low burden (LB). T-test and X² test were used to compare continuous and categorical variables. Survival analysis was performed using KM method and log-rank test. Results. At diagnosis, median age was 50 years, Hct 55%, Hb 18 g/dL, WBC 10 x109/L and PLT 482 x109/L. 53 (71%) were male, 27 (37%) had symptoms, 15 (21%) had splenomegaly, 32 (44%) had ≥1 CV risk factor (CVRF). HB pts (n=25, 33%) had higher Hct (58 vs 53%, p>0.001), Hb (18.5 vs 17.6 g/dl, p=0.035), WBC (13 vs 9 x109/l, p>0.001) and splenomegaly rate (40 vs 11%, p=0.003), compared to LB pts (n=50, 67%), while age, CVRF, and symptoms were similar. With a median follow-up time of 8 yrs, 54 (72%) started cytoreduction: 20 due to age and 2 due to thrombosis, while 32 received EC due to leukocytosis (n=13), PHL intolerance/resistance (n=7), splenomegaly (n=5), thrombocytosis (n=5), and symptoms (n=2). EC need was more common in HB (16/25, 64%) vs LB (16/50, 32%, p=0.008), with a 10-yrs EC probability of 84% in HB and 41% in LB (Figure 1A, p<0.005). In total, 5 pts had thrombosis (2 DTV, 1 AMI, 1 TIA, 1 PAOD): 4/25 (16%) were HB and 1/50 (2%) was LB (p=0.020), with a shorter thrombosis-free survival among HB pts (Figure 1B, p=0.031). Disease progression occurred in 9 pts (6 MF, 3 AML), without difference between HB and LB. Four deaths were recorded (3 in HB and 1 in LB), with a trend towards an inferior OS in HB pts (p=0.130). Conclusion. HB (vs LB) pts showed higher myeloproliferation and splenomegaly rate at diagnosis, higher risk of EC and subsequent thrombosis. Considering the introduction of new agents with potential effect on JAK2 VAF in PV, EC might be considered in HB pts.