5 Factors Linked to Greater Chance of Polycythemia Vera Progression

Certain characteristics may help predict which patients with polycythemia vera are more likely to experience disease progression, according to the REVEAL study, which was presented at the 2024 European Hematology Association Congress.

Data from the prospective phase 4 trial were presented by Dr. Michael R. Grunwald, chief of the Leukemia Division at Atrium Health’s Levine Cancer Institute and director of the Transplantation and Cellular Therapy Program at Levine Cancer Institute in Charlotte, North Carolina.

“Five predictors of [polycythemia vera] progression were identified: disease duration, thrombotic event (also known as blood clot) history, [white blood cell count] count of greater than 11 × 109/L, hematocrit [HCT] level of 0.45 liters of cells per liter of blood (L/L) or lower, and [variant allele frequency]. However, HCT [level] of 0.45 L/L or lower may be confounded by disease duration and cytoreductive treatment covariates. These results provide additional support for the use of disease duration and elevated WBC and VAF as risk factors for disease progression and identify history of TEs as a potential novel risk factor,” Grunwald and coauthors wrote in a poster presentation of the findings.

At a median follow-up of 3.7 years, findings from REVEAL, which included 2,023 patients with polycythemia vera, showed that 6.7% of patients progressed to myelofibrosis (MF). Results from an analysis of one factor of patients with versus without progression revealed that significant variables consisted of time from polycythemia vera diagnosis to study enrollment, history of thrombotic events, HCT levels of 0.45 L/L or lower and white blood cell (WBC) count of greater than 11 × 109/L at enrollment.

Investigators noted that these variables remained significant in an analysis that considered multiple variables, including time from PV diagnosis to enrollment, history of thrombotic events, HCT levels and WBC count.

“At enrollment, patients with HCT at or less than 0.45 L/L versus >0.45 L/L had a significantly longer duration from [polycythemia vera] diagnosis, had higher [polycythemia vera] risk, and were more likely to be receiving hydroxyurea or other cytoreductive treatment, which potentially confounds the HCT at or under 0.45 L/L covariate. These confounders were not observed in patients with WBC greater than 11×109/L versus at or less than 11×109/L, disease duration, [thrombotic event] history, WBC count of greater than 11 × 109/L, HCT of 0.45 L/L or lower, and VAF,” Grunwald and coauthors noted.

The real-world, multicenter, REVEAL study examined data from patients treated in US community and academic centers between 2014 and 2019. Of the 2,510 patients included in the study, 2023 received a confirmed polycythemia vera diagnosis; of these patients, 1,524 had JAK2 p. V617F-positive disease, 365 had a doctor-reported JAK2 mutation and 134 had polycythemia vera confirmed by bone marrow aspirate/biopsy.

Among all patients with a confirmed diagnosis of polycythemia vera, the median age at enrollment was 68.0 years (range, 22 to 95); most patients were male (51.2%), White (89.1%), and treated in a community practice setting (82.6%). Patients who experienced disease progression (135 patients) experienced a median time from diagnosis to enrollment of 7.2 years (range, 0.0 to 34.1) and the median follow-up for these patients was 3.4 years (range, 0.0 to 4.9). Patients who did not experience disease progression (1,888 patients) had a median time from diagnosis to enrollment of 3.7 years (range, 0.0 to 38.5) and the median follow-up for these patients was 3.7 years (range, 0.0 to 5.0).

Among patients with disease progression versus without, polycythemia vera risk at enrollment was high in the majority of patients (85.9% versus 78.7%). Polycythemia vera treatments received at enrollment were watchful waiting (6.7% versus 5.5%), phlebotomy (blood draw; 17.8% versus 27.8%), hydroxyurea (oral treatment for WBC; 38.5% versus 31.1%), hydroxyurea plus phlebotomy (17.8% versus 27.3%) or other (19.3% versus 8.4%), respectively. Further, 29.6% versus 19.7% of patients had a history of thrombotic events at enrollment, respectively.

Additional findings from a subset analysis revealed that of patients with quantitative allele burden data available, VAF was a significant covariate, and variant allele frequency remained a significant covariate in multivariate analyses with a stepwise model. WBC count was excluded from the multivariate analysis models because variant allele frequency and WBC count of greater than 11 versus less than or equal to 11 × 109/L are confounded variables.

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