A randomized phase 3 trial of interferon-α vs hydroxyurea in polycythemia vera and essential thrombocythemia

Abstract

The goal of therapy for patients with essential thrombocythemia (ET) and polycythemia vera (PV) is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for patients with ET and PV at high risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment-naïve, high-risk patients with ET/PV. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (P = .80) at 12 months. At 24 to 36 months, CR was 20% to 17% for HU and 29% to 33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, whereas grade 3/4 adverse events were more frequent with PEG (46% vs 28%). At 12 months of treatment, there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment, PEG was more effective in normalizing blood counts and reducing driver mutation burden, whereas HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk patients with ET/PV. This trial was registered at www.clinicaltrials.gov as #NCT01259856.

Graphical abstract

Figure 1.

CONSORT diagram for participant flow by treatment arm.

Figure 2.

Mutational analysis of patients treated in MPD-RC 112 trial. (A) Oncoprint of baseline mutations and (B) mutation frequency of patients enrolled in the study.

Figure 3.

Kinetics of JAK2V617F allele burden of patients treated in the MPD-RC 112 trial. (A) Maximum change in JAK2V617F allele burden from baseline by response status. (B) JAK2V617F allele burden over time (*P < .05). Baseline (n = 117), 12-month (n = 97), and 24-month (n = 52) allele burden values were included in the mixed model.