Dr Gangat on Reducing JAK2 Allele Burden With Ruxolitinib or Ropeginterferon Alfa-2b in Polycythemia Vera

“It will be interesting to compare the reduction in JAK2 allele burdens with ruxolitinib vs ropeginterferon alfa-2b and see which one may be better. Ruxolitinib is a good agent if the patient has splenomegaly and has constitutional symptoms or itching—those can be alleviated.”

Naseema Gangat, MBBS, a professor of medicine and a consultant in hematology at Mayo Clinic, discusses the potential use of ruxolitinib (Jakafi) to reduce JAK2 allele burden as opposed to ropeginterferon alfa-2b-njft (Besremi) in patients with polycythemia vera (PV).

Ruxolitinib is an FDA-approved therapy for the treatment of patients with polycythemia vera, and is currently available in the second line for patients who are refractory or resistant hydroxyurea, a standard first-line therapeutic, Gangat began. When determining first-line treatment selection, factors, such as age, thrombosis history, and hematocrit control, are considered, she explained. A close competitor of hydroxyurea is ropeginterferon alfa-2b-njft, which was initially FDA-approved in November 2021, Gangat added.

Although ruxolitinib is typically used as second-line treatment, emerging data have revealed that both ruxolitinib and ropeginterferon alfa-2b-njft can reduce JAK2 burden, Gangat stated. Although comparisons have been made between ruxolitinib and ropeginterferon alfa-2b-njft, it would be interesting to compare the reduction in JAK2 allele burden with these respective agents to potentially determine which one is the preferred option, she emphasized.

Of note, ruxolitinib has demonstrated efficacy and symptom reduction in patients with PV who have splenomegaly, and can alleviate constitutional symptoms and itching, Gangat asserted.

These efficacy and safety data were reflected in the phase 3 RESPONSE trial (NCT01243944) and the phase 2 MAJIC-PV trial (ISRCTN61925716), of which most patients were treated with hydroxyurea, and a subset of patients were treated with an interferon-based therapy in the best available therapy (BAT) arm. In these studies, ruxolitinib demonstrated superior symptom and hematocrit control compared with best available therapies, ultimately reducing JAK2 allele burden, Gangat concluded.