Final results from the phase 2 COMBI II trial indicate that the combination of ruxolitinib and pegylated-interferon-α2a (peg-IFN) yields high remission rates in patients newly diagnosed with polycythemia vera (PV). The study, published in Blood Advances, suggests this combination could be a promising treatment option for myeloproliferative neoplasms.
The investigator-initiated, single-center trial involved 25 adult patients with newly-diagnosed PV, all of whom underwent pretreatment phlebotomies. High-risk patients (aged 60 or older, or with a prior thrombosis) also received hydroxyurea. The primary endpoint was safety, while secondary endpoints included complete remission (CR), peripheral blood count remission (PBCR), and bone marrow histologic remission (BMHR).
The median age of the patients was 70 years, and 56% were male. Baseline characteristics included a median of 3 phlebotomies from diagnosis to study entry, with 76% of patients considered high-risk, 20% having a prior thrombosis, and 12% presenting with splenomegaly. The median hemoglobin was 13.8 g/dL, the median hematocrit was 0.44, and the median variant allele fraction (VAF) of JAK2 V617F at baseline was 54%.
Remission Rates and Molecular Response
At 12 months, 52% of patients achieved remission, with 12% experiencing a CR. By 24 months, the overall remission rate was 56%, and the CR rate remained at 12%. The 12- and 24-month BMHR rates were 20% and 16%, respectively. The PBCR rate significantly increased from 24% at baseline to 88% at 12 months and 92% at 24 months.
The overall molecular response rate was 52% at 12 months, improving to 68% at 24 months. Although no patients achieved complete molecular remission, there was a significant decrease in the JAK2 V617 VAF (P < .001), indicating a substantial reduction in disease burden.
Safety and Tolerability
The majority of adverse events (AEs) were grade 1 or 2 in severity. Common AEs included anemia, fatigue, itching, joint pain, dizziness, and sensory neuropathy. The most common grade 3-4 AE was fatigue. Discontinuation of peg-IFN or ruxolitinib occurred in 12% and 16% of patients, respectively. Notably, there were no grade 3 or 4 hematologic events reported.
Clinical Implications
These findings suggest that the combination of ruxolitinib and low-dose peg-IFN is both efficacious and acceptably toxic for patients with newly-diagnosed PV. According to the researchers, this combination therapy may represent one of the most promising treatment options for patients with myeloproliferative neoplasms. The COMBI I trial previously demonstrated the efficacy and safety of this combination in patients refractory or intolerant to peg-IFN monotherapy and/or hydroxyurea, further supporting its potential in treating PV.
