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 polycythemia vera with low-dose pegylated interferon alfa-2 in combination with ruxolitinib.
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.
Click to read more about myelofibrosis.
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.
Exagamglogene Autotemcel Meets End Points in Severe Sickle Cell Disease, β-Thalassemia
December 7th 2023Two posters set to be presented at the 65th American Society of Hematology Annual Meeting & Exposition met their primary and secondary end points regarding exagamglogene autotemcel therapy for sickle cell disease and β-thalassemia.
Read More
Oncology Onward: A Conversation With Dr Shereef Elnahal, Under Secretary for Health
April 20th 2023Shereef Elnahal, MD, MBA, under secretary for health at the Veterans Health Administration (VHA), sat for a conversation with our hosts Emeline Aviki, MD, MBA, Memorial Sloan Kettering Cancer Center, and Stephen Schleicher, MD, MBA, Tennessee Oncology, that covered the cancer footprint of the VHA.
Listen
NCCN Guidelines Update Adds Momelotinib Below Ruxolitinib for High-, Low-Risk Myelofibrosis
November 21st 2023Momelotinib was given category 2A and 2B status for patients with high- and low-risk myelofibrosis (MF) and MF with anemia. However, ruxolitinib retains a higher category of recommendation as a treatment for patients with MF.
Read More
Exploring Payer Coverage Decisions Following FDA Novel Drug Approvals
May 3rd 2022On this episode of Managed Care Cast, Ari D. Panzer, BS, lead author and researcher, then at Tufts Medical Center—now at Duke University—discusses the findings from his team’s investigation into coverage decisions by health plan insurers of the 66 drugs approved by the FDA in 2018.
Listen
Odevixibat Safe for Alagille Syndrome Based on Hepatic Changes
November 8th 2023Pooled phase 3 data presented at North American Society for Pediatric Gastroenterology, Hepatology & Nutrition 2023 support the benefit-risk profile of the ileal bile acid transport inhibitor in treating the rare liver disease.
Read More
Contributor: How Patients and Caregivers Can Be a Catalyst for Rare Disease Innovation
November 5th 2023Patient input and experiences play a crucial role in advancing rare disease research and therapy development, as they help define the disease, inform clinical trial design, and influence regulators and payers' decisions, ultimately serving as catalysts for innovation in the field.
Read More