Rare Disease Report

Using Interferon‐α2 & Ruxolitinib Combination Therapy to Treat Myeloproliferative Neoplasms

OCTOBER 22, 2018
Rachel Lutz
Interferon‐α2 and ruxolitinib combination therapy shows promise in treating myeloproliferative neoplasms, according to recent preliminary findings.

Investigators from Denmark studied the combination therapy of ruxolitinib with interferon‐α2 in order to observe the effects in 50 patients with myeloproliferative neoplasms, a disorder that is characterized by chronic inflammation and a dysregulated immune system coupled with impaired tumor surveillance.

Ruxolitinib is an anti-inflammatory agent that has demonstrable benefits when used to treat low and intermediate risk myelofibrosis patients and polycythemia vera patients. Interferon‐α2 is used to reduce elevated blood cell counts and splenomegaly in patients with myeloproliferative neoplasms; however, although it has been shown to have antiproliferative and immunomodulatory effects that are useful in treating rare neoplasms, the drug can result in toxicity.

As such, a prospective, open-label, single-arm phase 2 trial, referred to as the COMBI study, is investigating the feasibility of treating patients with low- to intermediate-risk myelofibrosis or polycythemia vera with low-dose pegylated interferon‐α2 in combination with ruxolitinib. The investigators postulated that combination therapy consisting of these 2 agents could be more efficacious than monotherapy with either agent and combining the 2 agents could also potentially improve the tolerability of interferon‐α2.

The main objectives of the study were remission, complete hematologic response, molecular response, and toxicity. The majority of the patients included in the study were intolerant or resistant to interferon‐α2 as a monotherapy, according to the investigators.

For the study, patients were treated with either interferon‐α2a (45 μg) or interferon‐α2b (35 μg) once-weekly, administered subcutaneously, plus ruxolitinib 20 mg BID twice per day (BID) orally. However, the ruxolitinib dose depended on the patients’ platelet counts. They were visited for follow-ups at baseline, 2 weeks, 1 month, 3 months, and every 3 months after that, until the period of 24 months was completed, marking the end of the treatment. The interim analysis of the ongoing phase 2 trial includes safety and efficacy data from 12 months of follow-up.

Among a subset of polycythemia vera patients (n=32), the investigators determined that 9% achieved partial remission, while 44% reached complete hematologic response at 12 months of follow-up, while 39% of myelofibrosis patients (n=18) reached partial remission and 58% reached complete hematologic response.

“Limitations notwithstanding, our preliminary results are remarkable since few prior studies in myeloproliferative neoplasms have shown remission rates (by the revised definitions) of this amplitude at one year of follow‐up,” the investigators wrote.

The most common adverse event observed was hematologic toxicity, but it was managed by dose reduction. The investigators noted adverse symptoms associated with interferon‐α2 injection, such as flu-like symptoms and injection site reactions, as well as gastrointestinal symptoms. Thirty-seven serious adverse events were recorded in 23 patients, and 20% of the patients were forced to discontinue.

“The preliminary results from this study suggest that combination therapy with low‐dose interferon‐α2 and ruxolitinib is feasible and efficacious in patients with low and intermediate‐risk myelofibrosis and, to a lesser extent, in patients with polycythemia vera, including in patients who were unresponsive or intolerant to interferon‐α2 monotherapy,” the study authors concluded. “These results warrant phase 3 studies to assess the safety and efficacy of combination therapy compared to current standard treatment modalities as well as a study with combination therapy in patients with newly diagnosed PV or low and intermediate‐risk myelofibrosis.”

The study was published in Cancer Medicine and was conducted as part of ongoing research in the COMBI trial, in which investigators are evaluating the safety and efficacy of combination therapy with low dose interferon‐α2 and ruxolitinib in patients in Denmark. The study began in June 2014 and is ongoing; treatment duration will be maximum 24 months.

The investigators also wrote that this is the first combination therapy study examining interferon‐α2 and ruxolitinib in polycythemia vera and low and intermediate risk myelofibrosis patients.

Stay informed on the latest rare disease news and developments by signing up for our newsletter.
Copyright © RareDR 2013-2018 Rare Disease Communications. All Rights Reserved.