According to research published in Blood, both pegylated interferon-alpha (PEG) and hydroxyurea (HU) appear to be efficacious treatments for essential thrombocythemia (ET) and polycythemia vera (PV) and did not differ in limiting thrombotic events and disease progression. With longer treatment, PEG appeared to be more effective in normalizing blood counts and reducing driver mutation burden, while HU appeared to induce more histopathologic responses.

The findings are from The Myeloproliferative Disorders Research Consortium 112, an investigator-initiated, phase 3 trial comparing PEG with HU in treatment naïve patients with high-risk ET/PV (ClinicalTrials.gov Identifier: NCT01259856), conducted by researchers at 24 North American and European sites. An intention-to-treat evaluation was performed at 12, 24, and 36 months, and the primary endpoint was the 12-month complete response (CR) rate. Exploratory analysis included mutational status (JAK2, CALR, ASXL1, and TET2), variant allele frequency (VAF) over time, and association of treatment, disease type, and mutational status with CR.

A total of 168 patients (median age, 61 years; range, 18-87) were randomly assigned (1:1) to receive PEG (n=82) or HU (n=86), stratified by disease type (ET, n=81; PV, n=87). Mutations in JAK2 were most frequent (91%), followed by CALR (8%) and MPL (3%). The median baseline JAK2V617F VAF was 13% and 35% in patients with ET and PV, respectively. Patients were treated for a median of 81.0 weeks.


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The 12-month CR rate was 35% with PEG and 37% with HU (P =.80). The 24-and 36-month CR rates were 29% and 33% for PEG and 20% and 17% for HU, respectively. The investigators observed greater reductions in JAK2V617F with PEG and more frequent histopathologic responses with HU.

At 24 months, the cumulative incidence of thrombosis was 2% (95% CI, 0.3-15) with PEG and 2% (95% CI, 0.3-13) with HU. Disease progression occurred after 46 months in 1 patient treated with HU. After 9 months, 1 patient treated with HU died of lung cancer. Grade 3/4 adverse events were reported in 46% of patients treated with PEG and 28% of patients treated with HU.

The power was impacted by early study closure (after the accrual of 168 patients instead of the targeted 300) due to the manufacturer halting PEG access.

Disclosure: This research was supported by Roche Genentech. Please see the original reference for a full list of disclosures.

Reference

Mascarenhas J, Kosiorek HE, Prchal JT, et al. A randomized, phase 3, trial of interferon-α versus hydroxyurea in polycythemia vera and essential thrombocythemia. Blood. Published online January 10, 2022. doi:10.1182/blood.2021012743