Interferon in Polycythemia Vera (PV) Yields Improved Myelofibrosis-Free and Overall Survival

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.2942-2942
• Main Authors: Abu Zeinah, Ghaith, Krichevsky, Spencer, Jaber, Diana, Savage, Niamh, Sosner, Claudia, Hoberman, Gabriela, Ritchie, Ellen K., Schafer, Andrew I., Scandura, Joseph, Silver, Richard T.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-130265

Introduction: The progression of polycythemia vera (PV) to myelofibrosis (MF) is associated with significant morbidity and mortality. Interferon alfa (rIFNa), a disease-modifying agent, has potential to delay or prevent post-PV MF and improve overall survival but supporting data are required. We present results of the largest study demonstrating improved myelofibrosis-free and overall survival (MFS and OS) of rIFNa treated PV patients (pts) compared to other PV pts. Objectives: To estimate the MFS and OS of treated PV pts and determine the relative risk for post-PV MF and mortality of those treated with rIFNa compared to those treated with other standard therapy. Methods and Study Design: To ensure sufficient follow-up for analysis of long-term outcomes, this IRB approved study identified all adult pts treated at our center from 1974-2019 according to PVSG criteria (1974-2007), our published criteria (2008-2016) and WHO criteria (2016-2019) using a standardized query of electronic medical records. Demographic data, clinical characteristics, treatment history and outcomes were collected. The extended follow-up of this large PV cohort permitted us to evaluate the effectiveness of PV therapy using both intention-to-treat (ITT) and treatment duration (on-treatment) analyses. In the ITT analysis, pts were assigned to rIFNa or hydroxyurea (HU) arms according to the first cytoreductive treatment they received for at least one year or to phlebotomy only (PHL-O) if no cytoreductive treatment was given. On-treatment analysis was performed to account for cross-over and assess how duration of a given therapy influenced outcomes. The onset of post-PV MF was defined by IWG-MRT criteria. MFS and OS were estimated using Kaplan-Meier methods and the log-rank test compared survival between treatment arms in ITT analysis. Multivariate analysis of post-PV MF risk and mortality was performed using a Cox proportional hazards model. The model accounts for age at diagnosis and is stratified by treatment arms (ITT) or by treatment as a time-dependent covariate (on-treatment). Results: We identified 306 PV pts whose median age at diagnosis was 54 years (yr) (range 20-91) and of whom 151 (49%) were women. The median follow-up was 11 yr (range 1-45). The first line treatment was rIFNa in 75 (25%), HU in 134 (44%) or other cytoreductive regimens in 37 (12%). PHL-O was instituted in 60 pts (20%). Treatment cross-over occurred in 82 pts (27%), with the least from rIFNa arm (22%) (Table2