Combination Therapy With Interferon Alfa-2 and Ruxolitinib Shows Promise in Treating Myeloproliferative Neoplasms

Interferon alfa-2 can reduce elevated blood cell counts and splenomegaly in patients who have myeloproliferative neoplasms (MPNs), including myelofibrosis and polycythemia vera (PV). However, while interferon alfa-2 has antiproliferative and immunomodulatory effects that are useful in treating these rare neoplasms, the drug can result in toxicity and is subject to a 10% to 30% discontinuation rate.

The COMBI study, a prospective, open‐label, single‐arm phase 2 study ongoing in Denmark, is investigating the feasibility of treating patients with low- to intermediate-risk myelofibrosis or PV with low-dose pegylated interferon alfa-2 in combination with ruxolitinib. The patients (n = 51) in the study will be treated for a maximum of 24 months, and an interim analysis, at 12 months of follow-up, was recently published in Cancer Medicine.

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The primary end point of the study is complete remission (CR) or partial remission (PR) assessed at 12 months (reported in the current paper) and at 24 months (the final analysis). The patients, 32 with PV and 18 with myelofibrosis, were treated with once-weekly pegylated interferon alfa-2, using either 45 mcg of the brand name drug Pegasys or 35 mcg of the brand name drug PegIntron. All patients were also given 20 mg of ruxolitinib twice per day.

At 12 months, no patients with PV achieved CR, but 3 patients (9%) achieved PR. However, 3 patients with myelofibrosis (17%) achieved CR, and PR was achieved by another 4 patients (22%). One patient with myelofibrosis died from transformation to acute myeloid leukemia.

The most commonly reported adverse events (AEs) were anemia, leukopenia, and neutropenia, all of grade 1 or grade 2. One patient experienced thrombocytopenia of grade 3 or above. Nonhematologic AEs included arthralgia or myalgia, as well as injection reactions and gastrointestinal symptoms. Thirty‐seven serious AEs were recorded in 23 patients, and the discontinuation rate was 20%.

“Our preliminary results are remarkable since few prior studies in MPN have shown remission rates…of this amplitude at [1] year of follow‐up,” write the authors, who conclude that using low-dose pegylated interferon alfa-2 together with ruxolitinib is both feasible and efficacious in treating MPNs and call for phase 3 studies to compare the combination treatment with the currently used standard treatment.

Reference

Mikkelsen SU, Kjær L, Bjørn ME, et al. Safety and efficacy of combination therapy of interferon-α2 and ruxolitinib in polycythemia vera and myelofibrosis. Cancer Med. 2018;7(8): 3571-3581. doi: 10.1002/cam4.1619.