P206 | Impact of Eln Clinical Signs and Symptoms on Outcome in Polycythemia Vera Patients Treated With Hydroxyurea or Ruxolitinib: a Cooperative Study
Year: 2025
Type: article
Abstract: 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.
Authors: C. Sartor, A. Dedola, A. Iurlo, E. Rossi, M. Breccia, E.M. Elli, E. Morsia, R. Latagliata, N. Pugliese, F. Mendicino, A. Tieghi, G. Benevolo, G. Binotto, B. Martino, M. Farina, A. D’addio, M. Tiribelli, D. Cilloni, M. Crugnola, G. Caocci, D. Cattaneo, F. Cavalca, E. Scalzulli, F. Pane, G.A. Palumbo, F. Branzanti, V. De Stefano, F. Palandri
Institutions: Istituto di Ematologia di Bologna, University of Bologna, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Agostino Gemelli University Polyclinic, Sapienza University of Rome, Marche Polytechnic University, Federico II University Hospital, University of Naples Federico II, Ospedale di Belcolle, Ospedale Annunziata di Cosenza, Ospedale SS. Annunziata, Azienda Sanitaria Unità Locale di Reggio Emilia, Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, University of Padua, Azienda ospedaliera "Bianchi-Melacrino-Morelli", Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, University of Brescia, Azienda Unità Sanitaria Locale Della Romagna, University of Udine, University of Turin, University of Cagliari, University of Catania
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093123637
FWCI:
Cites:
Cited by:
Related to: