MPN-RC 112 Clinical Trial Fails to Confirm Interferon Superiority in PV and ET

-edited

Research suggests conflicting results with Interferon treatment of polycythemia vera and essential thrombocythemia.

by Dr. C.H. Weaver M.D. updated 5/2019

Hydroxyurea is currently an initial treatment of choice for individuals with high risk essential thrombocythemia (ET) and polycythemia vera (PV) who require treatment. Pegylated interferon (PEG) is widely used outside the United States and is advocated as an alternate option due to its “success” in Europe and its proposed potential to modify the disease course in PV patients.

Interferon belongs to a group of agents called cytokines that produce their anti-cancer effects by stimulating the immune system to help fight the cancer. Interferon is not a precision cancer medicine but works in a very general manner and is thus associated with several systemic side effects including fatigue, weakness, fever, chills, muscle pain, headache, and irritability.

In order to evaluate peg-interferon the MPN–RC 112 clinical trial was designed and conducted by the Myeloproliferative Neoplasms Research Consortium to compare hydroxyurea to pegylated interferon in patients with high-risk ET/PV. The primary end point being of the study was to compare the complete remission (CR) rate at 12 months. (1)

The final analysis of the MPN–RC 112 trial has now been reported and the CR rates in patients with high-risk ET/PV at 12 and 24 months were found to be similar for peg-interferon and hydroxyurea. Furthermore, pegylated interferon was associated with a higher rate of significant side effects when compared to hydroxyurea.

These trial results are in contrast to the results of the PROUD-PV study conducted in Europe, which demonstrated the superiority of PEG interferon when compared to hydroxyurea in patients with PV. After 24 months of treatment there was a 77.6% CR rate for PEG compared to 55.9% for hydroxyurea. (2)

The reasons for the different results are not immediately apparent but it may be be that longer follow-up is needed to demonstrate superiority of interferon to hydroxyurea in the MPN–RC 112 trial.

Currently in the United States, hydroxyurea is readily available, very inexpensive and ~ 70% of patients who receive hydroxyurea will not need any additional therapy. Interferon is associated with some challenges because it is not FDA-approved for PV and is more expensive. Acquiring it through insurance may takes multiple attempts and is it not always approved for use.

Other Ongoing Trials Evaluating Interferon

Daliah Phase 3 clinical trial failed to demonstrated superiority of IFN or HU but reported that the reduction in JAK2V617F allele burden was greater with IFN therapy.(3)

PROUD and CONTI-PV studies of Ropgeinteferon revealed that Ropeginteferon provided durable hematologic responses and symptom control, was well tolerate and 66% of patients achieved a molecular remission for JAK2 as well as a reduction in other disease associated genes such as TET2.(4)

References:

  1. Mascarenhas J, Kosiorek HE, Prchal J, et al. Results of the Myeloproliferative Neoplasms - Research Consortium (MPN-RC) 112 randomized trial of pegylated interferon alfa-2a (peg) versus hydroxyurea (hu) therapy for the treatment of high risk polycythemia vera (PV) and high risk essential thrombocythemia (ET). Presented at: 2018 ASH Annual Meeting; December 1-4, 2018; San Diego, CA. Abstract 577.

  2. Gisslinger H. et. al. COMPARISON OF LONG-TERM EFFICACY AND SAFETY OF ROPEGINTERFERON ALFA-2B VS. HU IN POLYCYTHEMIA VERA PATIENTS AGED BELOW OR ABOVE 60 YEARS: TWO-YEAR ANALYSIS FROM THE PROUD/CONTINUATION PHASE III TRIALS. Jun 15, 2018; 214443.

  3. Knudsen T, Hansen D, Ocias L, et al. Long-Term Efficacy and Safety of Recombinant Interferon Alpha-2 Vs. Hydroxyurea in Polycythemia Vera: Preliminary Results from the Three-Year Analysis of the Daliah Trial - a Randomized Controlled Phase III Clinical Trial. Abstract 580. Presented at the 2018 Annual Meeting of the American Society of Hematology. December 3rd. San Diego, CA.

  4. Gisslinger H, Klade C, Georgiev P, et al. Evidence for Superior Efficacy and Disease Modification after Three Years of Prospective Randomized Controlled Treatment of Polycythemia Vera Patients with Ropeginterferon Alfa-2b Vs. HU/BAT. Abstract 579.Presented at the 2018 Annual Meeting of the American Society of Hematology. December 3rd. San Diego, CA.

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