Hydroxyurea Versus Pegylated IFN-α in Patients with Essential Thrombocythemia and Polycythemia Vera

Take-aways:

• Rates of thrombosis and progression were low in essential thrombocythemia (ET) and polycythemia vera (PV) treated with hydroxyurea (HU) or pegylated interferon-α (IFN-α).
• In PV, pegylated IFN-α was more effective than HU in normalizing blood counts and reducing JAK2V617F variant allele frequency.
• Compared with pegylated IFN-α, HU induced more histopathologic responses in patients with ET.

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In patients with high-risk essential thrombocythemia (ET) and polycythemia vera (PV), both hydroxyurea (HU) and pegylated interferon-α (IFN-α) were effective in normalizing blood counts and reducing thrombotic events. This is according to research published in Blood.

“The continued controversy over the choice of drug for first-line therapy of ET or PV patients at an increased risk for developing thrombotic events is a consequence of the limited numbers of randomized trials performed and the chronic nature of these malignancies limiting the number of thrombotic events that occur during follow-up,” the authors, led by John Mascarenhas, MD, of the Icahn School of Medicine at Mount Sinai in New York, wrote.

Currently, HU and pegylated interferon-α represent the most frequently used cytoreductive therapies for patients with ET and PV who are at high risk for vascular complications. In this analysis, researchers reported findings from the phase III Myeloproliferative Disorders Research Consortium 112 trial, which enrolled 168 patients with treatment-naive ET (n, 81) and PV (n, 87).

The majority of patients (82% with PV and 75% with ET) were deemed high-risk because of age older than 60 years and/or a history of thrombosis. The most frequent myeloproliferative neoplasm driver mutations were JAK2V617F (91%), CALR (8%), and MPL (3%). Common co-occurring mutations were TET2 (24%) and ASXL1 (9%). At baseline, the median JAK2V617F variant allele frequency (VAF) was 13% in patients with ET and 35% in patients with PV.

Patients were randomized to receive HU (n, 86) or pegylated IFN-α (n, 82).

Investigators performed intention-to-treat evaluations at 12, 24, and 36 months, with patients achieving at least a partial hematologic response remaining on treatment. Length of therapy was determined according to time of enrollment; the first subjects enrolled were eligible to receive therapy for up to 64 months, while the last could receive therapy for a maximum of 12 months. Median treatment duration was 81 weeks and 94.6 weeks for patients receiving HU and pegylated IFN-α, respectively.

The study’s primary endpoint was the rate of complete response (CR) at 12 months. In patients treated with HU, the CR rate at 12 months was 37%, compared with 35% for patients treated with pegylated IFN-α (P = .80).

In the pegylated IFN-α arm, median JAK2V617F VAF decreased consistently from baseline through month 24, while median JAK2V617F VAF increased in patients treated with HU after month 12. Additionally, in patients treated with pegylated IFN-α, the percentage of patients with PV who achieved hematocrit control at 12 months was higher than observed in patients with ET (65% vs. 43%). These findings suggest that “[pegylated IFN-α] may be more effective in correcting blood counts in PV as compared to ET,” the authors wrote.

Grade 3 or higher adverse events (AEs) were reported in a total of 60 patients (37%) overall. In the HU group, 22 patients (28%) experienced a grade 3 or higher AE, versus 38 patients (46%) with pegylated IFN-α.
“Our data indicate that pegylated IFN-α and HU are both effective treatments for PV and ET at 12 months without significant difference in CR,” the authors concluded. “The decision to choose one agent over the other must be personalized.”

Disclosures: This research was supported by the Myeloproliferative Disorders-Research Consortium, the National Cancer Institute, and Roche Pharma AG. Study authors report financial relationships with Merck, the manufacturer of pegylated IFN-α, and Bristol Myers Squibb, the manufacturer of hydroxyurea.

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. 2022 Jan 10;blood.2021012743. [Epub ahead of print]