P214 | PROGNOSTIC IMPACT OF EARLY SPLEEN RESPONSE IN POLYCYTHEMIA VERA PATIENTS TREATED WITH RUXOLITINIB: A REAL-WORLD COOPERATIVE STUDY

Ruxolitinib (RUX) is indicated for patients (pts) with Polycythemia Vera (PV) who are resistant/intolerant to hydroxyurea. To investigate early predictors of long-term outcome, we conducted a sub-analysis of the multicenter Italian “PV-ARC” study (NCT06134102), including 218 PV pts treated with 2^nd-line RUX. The primary and secondary outcomes at 3 months were the spleen response (SR50: ≥50% reduction if spleen palpable ≥5cm below costal margin; no palpable spleen if spleen <5cm) and the complete hematological response (CHR: WBC<10×10⁹/L, PLT<400×10⁹/L, HCT<45% and no phlebotomy), respectively. Their association with overall (OS), thrombosis-free (TFS), myelofibrosis-free (MFS) and event-free survival (EFS: including all 3 events) was evaluated by KM analysis with delayed entry. At RUX start, 113 pts (51.8%) had palpable splenomegaly (≥5cm in 52 pts); 41.3% had HCT>45% and/or required phlebotomies; 46.3% had WBC≥10×10⁹/L; 47.4% had PLT≥400×10⁹/L; 61.9% of pts had itching (mean score: 3.6). At 3 mos, 53/113 (46.9%) and 51/218 (23.4%) evaluable pts achieved SR50 and CHR, respectively; 11 (9.7%) pts had a double response (CHR+SR50). 105 (48.2%) additional pts had no palpable spleen at baseline and at 3 mos. After a mean RUX therapy of 3.4 yrs, 7 pts had a thrombosis, 18 died, and 27 pts progressed to post-PV MF, for a 5-yr TFS, OS, MFS and EFS of 96.6%, 92.1%, 82.4% and 73.3%, respectively. 5-yr EFS was significantly longer in pts without baseline splenomegaly (86.1%). Pts achieving a SR50 had better EFS (74.0%) compared to no-spleen responders (noSR50: 53.0%), with an HR (SR50 vs noSR50) of 0.47 (95% CI: 0.23–0.95, p=0.037) (Figure 1, global log-rank p=0.001). Analyzing individual events, no baseline splenomegaly and SR50 achievement were also significantly associated with improved 5-yr MFS compared to non-responders (no splenomegaly: 94.5%, SR50: 83.6%, noSR50: 62.4%, log-rank test p<0.001); HR (SR50 vs noSR50): 0.20, p<0.001). Conversely, CHR was not associated with improved 5-yr EFS (73.0% vs 74.3% in noCHR pts, p=0.58) and MFS (82.0% vs 82.5% in noCHR pts, p=0.52). No differences in OS and TFS were observed by SR50, CHR, or by double response. At 3 mos, 77/135 evaluable pts had a ≥50% reduction in the itching score. This did not correlate with SR50, CHR or outcomes. Early SR50 is associated with long-term benefit in PV pts receiving 2^nd-line RUX. Its evaluation may allow for closer monitoring of disease progression and timely treatment decisions.