Interferon-Alpha Reduces Myelofibrosis Risk, Mortality Rate in Low- and High-Risk Polycythemia Vera

Interferon-alpha (IFN) can delay and possibly prevent post-PV myelofibrosis (MF) and improve survival in patients with polycythemia vera (PV), according to data from a single-center, retrospective study that were presented during the 2020 ASH Annual Meeting and Exposition.

In a time-on-treatment multivariable analysis, IFN reduced the risk of myelofibrosis by 9% per year on IFN (HR, 0.91; 95% Ci, 0.87-0.95; P < .001) and reduced overall mortality by 6% per year on IFN (HR, 0.94; 95% CI, 0.90-0.99; P = .012), independent of age, sex, thrombosis history, cardiovascular risk factors, or other treatments, said presenter Ghaith Abu-Zeinah, MD, in a virtual presentation during the meeting.

Moving forward, the data suggest that guidelines should consider IFN in high- and low-risk PV, he emphasized.

“Despite the progress we have made in treating PV, we have not seen a significant improvement in OS over the past few decades,” said Abu-Zeinah a hematologist/oncologist at Weill Cornell Medicine, adding that patients with PV have shortened survival. “This brings up an unmet need for identifying life-prolonging therapies in PV. IFN comes to mind as a disease-modifying therapy in PV…because in some cases it leads to complete bone marrow responses [as high as 26%],” he said. In some patients, bone marrow fibrosis is reversed with IFN treatment.

To assess survival outcomes in patients with PV treated with IFN, Abu-Zeinah and colleagues performed a single-center retrospective study at Weill Cornell Medicine in which 470 patients diagnosed with PV between 1966 and 2019 were identified by a query of the electronic medical record system. Patients with PV were included if they met the Polycythemia Vera Study Group criteria, Weill Cornell Medicine criteria, and the World Health Organization 2016 criteria for a diagnosis of PV. Patients had a median duration of follow-up of 10 years, with a range up to 45 years.

The median age was 54 years—“younger than that reported previously,” he said. Forty-four percent were high risk according to European LeukemiaNet (ELN). Ninety-three patients were initially treated with IFN, defined as those who received it as a first-line treatment for at least 1 year; 189 were treated initially with hydroxyurea (HU); and 133 were on phlebotomy only throughout the course of follow-up. The IFN group was significantly younger (P < .001) than those in the other 2 groups; the percentage with cardiovascular risk factors was significantly lower in the phlebotomy-only group (P = .002); and there were significantly fewer ELN high-risk patients in the IFN group (P < .001), primarily as a function of age, he said.

In an intent-to-treat analysis, IFN was associated with improved OS in high-risk PV, with a 20-year OS probability of 66% in the IFN group, 40% in the HU group, and 14% in the phlebotomy-only group (P = .016). The rate of myelofibrosis-free survival (MFS) of high-risk patients was similarly higher in patients treated with IFN, with a 20-year probability of 89%, compared with the HU group (41%) and the phlebotomy-only group (36%) but the differences did not achieve significance (P = .19) because the study was not powered for this.

The rate of MFS of low-risk patients was significantly higher in those treated with IFN (84%) than in the HU (65%) and phlebotomy (55%) groups (P = .0011). The 20-year OS of low-risk patients was also higher, but not significantly so, in the IFN group (100%) compared with 80% and 85% in the HU and phlebotomy-only groups, respectively (P = .44).

Current guidelines from the National Comprehensive Cancer Network and ELN recommend phlebotomy-only as initial treatment in low-risk patients and either HU or IFN in high-risk patients. “What we are proposing is considering IFN as a long-term management strategy in patients with lower-risk PV, and considering IFN over HU in patients with high-risk [PV], given our data and ongoing data from maturing clinical trials,” he said.

Reference

Abu-Zeinah G, Krichevsky S, Cruz T, et al. Interferon in polycythemia vera (PV) yields improved myelofibrosis-free and overall survival. Presented at: 2020 ASH Annual Meeting and Exposition; December 4-8, 2020; virtual. Abstract 480.