Pegylated recombinant interferon alfa-2a is effective for patients with high-risk essential thrombocythemia (ET) or polycythemia vera (PV) who discontinued previous therapy with hydroxyurea, according to study results published in Blood.
Complications related to a diagnosis of ET and PV, Philadelphia chromosome-negative myeloproliferative neoplasms, include bleeding and/or thrombosis and are due to the presence of varying degrees of erythrocytosis and thrombocytosis. Other potential clinical manifestations of these diseases include splenomegaly, as well as potential risks of disease transformation to primary myelofibrosis or acute myeloid leukemia.
Although hydroxyurea is considered a first-line cytoreductive therapy for patients with ET and PV at high risk for vascular complications, some patients have disease that is resistant to this therapeutic approach or are intolerant of treatment with hydroxyurea.
In this prospective, nonrandomized, open-label, phase 2 trial (ClinicalTrials.gov Identifier: NCT01259817), 115 patients with ET (n=65) or PV (n=50) from the Myeloproliferative Disorders Research Consortium who were resistant to (32.5%) or intolerant of (67.5%) hydroxyurea received salvage therapy with pegylated recombinant interferon alfa-2a administered subcutaneously with increasing monthly dose titrations to a maximum dose of 180 mcg weekly.
Baseline characteristics of these patients, such as prior thrombosis in 32.2% and 22% of patients with ET and PV, respectively, and splenomegaly in 34.8% of the overall study population, were consistent with high-risk disease. Approximately half of patients with ET and nearly all patients with PV had disease characterized by a JAK2V617F mutation. In addition, more than one-third of patients with ET had CALR-positive disease.
At 12 months, complete (CR) and partial response (PR) rates were observed in 43.1% and 26.2%, respectively, of the intention-to-treat (ITT) population of patients with ET. In the ITT population of patients with PV, the corresponding response rates were 22% and 38%. Patients with CALR-mutated ET had significantly higher CR rates compared with those with disease characterized by CALR wild-type ET (56.5% vs 28.0%; P =.01).
Notably, no major bleeding events occurred over the course of the study. Disease transformation to myelofibrosis occurred in 1 patient with PV, and 1 patient with ET with a baseline biopsy consistent with prefibrotic myelofibrosis had disease progression to acute myeloid leukemia.
Regardless of attribution, any grade adverse events occurred in more than 90% of patients, with 43.8% of patients experiencing grade 3 or higher adverse events. Nearly three-quarters of patients continued treatment for more than 12 months, and only 13.9% of patients discontinued treatment due to an adverse event.
Although global health status (GHS)/quality of life (QOL) assessments showed significant improvements in symptoms related to ET or PV, symptoms related to treatment with pegylated recombinant interferon alfa-2a, such as flu-like symptoms and blurry vision, also increased significantly. Nevertheless, for those able to tolerate treatment with pegylated recombinant interferon alfa-2a, GHS/QOL remained relatively stable.
“In the setting of hydroxyurea resistance or intolerance, pegylated recombinant interferon alfa-2a has demonstrated activity in high-risk ET and PV patients and should be considered an effective therapeutic choice,” the study authors commented in their concluding remarks. “Proper patient selection, gradual dose escalation, and prompt evaluation and management of adverse effects can increase the efficacy and tolerability of pegylated recombinant interfereon alfa-2a in ET and PV patients.”
Yacoub A, Mascarenhas J, Kosiorek H, et al. Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea [published online September 12, 2019]. Blood. doi: 10.1182/blood.2019000428