Novel Approaches to Treating Polycythemia Vera Needed, Say Researchers

Additional efforts are warranted to develop promising novel treatments for polycythemia vera (PV), said researchers of a review, highlighting a need to define the best treatment approach for the chronic myeloproliferative neoplasm.

The current treatment landscape of PV hinges on treatments like hydroxyurea (HU) and ruxolitinib, the latter having emerged as an effective second-line therapy in patients with severe pruritis, symptomatic splenomegaly, or post-PV myelofibrosis symptoms.

There are also investigational drugs being assessed in trials with the aim of reducing thrombosis events and reducing symptom burden, although much of these potential treatments have fallen short in clinical trials, wrote the researchers.

“Many emerging treatments have been evaluated in the last years, especially for HU resistant patients. Unfortunately, conclusive results are still lacking,” wrote the researchers, noting that many trials of novel treatments for PV have failed to demonstrate significant repose improvements and alleviation of symptoms. “At present, givinostat seems to be the most promising novel drug and a phase III trial is ready to start in the near future. Givinostat complete clinical trials results will be available in the next years.”

Givinostat, an oral treatment that inhibits class I and II HDACs, has been evaluated in several trials, demonstrating efficacy and tolerability among patients with PV, including a pilot phase 2A study of 29 patients with JAK2 V617F-positive MPN. Among the 12 patients with PV, the treatment demonstrated 1 complete response and 6 partial responses. There were 2 patients who discontinued treatment. Among the other 10 patients, 7 (70%) achieved phlebotomy-free status, 7 (70%) had had resolved splenomegaly, and 9 (90%) had resolved pruritus. The study showed no severe toxicities with the treatment.

Following the phase 2A study, a randomized phase 2 study of 44 patients with PV resistant to HU added givinostat 50 mg once or twice daily to HU treatment. Throughout the study, 55% of patients receiving givinostat once daily achieved responses and 50% of patients receiving givinostat twice daily achieved responses while 64% and 67% achieved pruritus control, respectively. Less than 5% of patients experienced grade 3 adverse events (AEs) and no patients experienced grade 4 AEs.

A multicenter trial confirmed the findings of the previous 2 studies, showing complete and partial responses among 45 patients receiving the treatment for a median of 4 years. The study also showed a reduction of Hct below 45% without phlebotomy and a normal spleen size in over half (56%) of patients. Similar to the phase 2 study, there were no grade 4 toxicities observed.

Reference

Benevolo G, Vassallo F, Urbino I, Giai V. Polycythemia vera (PV): Update on emerging treatment options. Ther Clin Risk Manag. 2021;17:209-221.