P206 | IMPACT OF ELN CLINICAL SIGNS AND SYMPTOMS ON OUTCOME IN POLYCYTHEMIA VERA PATIENTS TREATED WITH HYDROXYUREA OR RUXOLITINIB: A COOPERATIVE STUDY

ELN-defined clinical signs and symptoms (CSSs) identify a high thrombotic risk phenotype in Polycythemia Vera (PV) patients (pts) treated with hydroxyurea (HU) (Palandri et al, Blood. 2024; 144(S1):242). It is unclear if CSSs may influence the thrombotic risk during ruxolitinib (RUX) and what impact they may have on the risk of PV progression into secondary myelofibrosis/acute leukemia (SMF/AL) in HU and RUX-treated pts. To address these issues, we conducted a sub-analysis of the multicenter Italian “PV-ARC” study (NCT06134102), including 739 pts treated with 1st-line HU and 254 treated with 2nd-line RUX. Incidence ratio rates (IRRs) per 100 patient-years (%p-y) of thrombosis and progression to SMF/AL were calculated. Thrombosis-free survival (TFS) and progression-free survival (PFS) were estimated using delayed-entry KM analysis. Overall, 189 (19.0%) pts were low risk (LR) (age<60 yrs and no previous thrombosis; HU: 18.5%; RUX: 20.5%). At therapy start, CSSs were present in 443 (60.0%) HU pts and in 165 (65.0%) RUX pts, comparably across thrombotic risk categories. During a mean treatment duration of 5.7 yrs (HU) and 3.2 yrs (RUX), 72 (HU) and 8 (RUX) pts had a thrombosis, while 70 (HU) and 34 (RUX) pts progressed to SMF/AL. In HU pts, the IRR of thrombosis was 1.7%p-y, and significantly greater in CSSs pts (2.2 vs 0.7%p-y in no-CSSs, p<0.001). In RUX pts, CSSs confirmed association with thrombotic risk (1.5 vs 0% p-y in no-CSSs, p=0.04); the IRR of thrombosis was lower compared to HU pts (1.0 %p-y). HU pts had an IRR of progression to SMF/AL significantly lower than RUX pts (1.6 vs 4.2%p-y, p<0.001), and CSSs were not associated with disease progression (1.7 vs 1.3%p-y in no-CSSs, p=0.38). Conversely, during RUX therapy, CSSs pts had higher rates of SMF/AL than no-CSSs pts (5.3 vs 2.2%p-y, p=0.04). At 5 years, TFS was 88.7% (HU) and 95.4% (RUX) in CSSs pts compared to 96.1% and 100% in no-CSSs (p<0.001); PFS was 94.4% (HU) and 74.9% (RUX) in CSSs pts vs 97.2% and 90.0% in no-CSSs (p<0.001) (Fig. 1). Analyzing individual CSSs, progressive splenomegaly in HU pts (HR: 5.3, p=0.002) and persistent leukocytosis in RUX pts (HR: 1.93, p=0.045) were associated with progression to SMF/AL. ELN-defined CSSs influence the thrombotic risk in both HU and RUX-treated pts. Also, CSSs predict progression into SMF/AL in advanced pts requiring 2nd-line RUX. CSSs assessment may improve risk stratification and optimize treatment monitoring in PV.