Greater Understanding of PV, ET Drives Potential New Treatment Options

The novel agents are a result of a greater understanding of the conditions and may modify the diseases’ course and cytoreduction, researchers said.

A pair of researchers highlighted potential treatment approaches for polycythemia vera (PV) and essential thrombocythemia (ET), including the development of novel agents and optimization of current options.

The novel agents, said the researchers, are a result of a greater understanding of the conditions and may modify the diseases’ course and cytoreduction.

“Targeting of epigenetic pathways, particularly the varied status of post-translational histone acetylation/de-acetylation which contribute to the regulation of gene transcription critical to cell cycling, offer a promising therapeutic opportunity,” wrote the pair.

“The histone deacetylase inhibitors (HDACis) are theorized to reverse histone/DNA complex compaction and thus open the chromatin structure to restore pro-apoptotic gene transcription. Although an oversimplified view, the HDACis are hypothesized to have a role in the treatment of myeloproliferative neoplasms (MPN),” they said.

According to the researchers, there have been 3 HDACis—vorinostat, panobinostat, and givinostat—that have demonstrated an ability to suppress proliferation and induce apoptosis of JAK2-mutated MPN cells.

MDM2 inhibitors are also being studied for use in PV. In a phase 1 trial, oral MDM2 antagonist idasanutlin resulted in a favorable toxicity profile among 13 patients with high-risk PV and ET who were previously treated. More than half (58%) of patients achieved a complete or partial response.

More data from an interim analysis of a phase 2 study showed that the treatment helped 9 of 16 patients with hydroxyurea-resistant or intolerant PV achieve hematocrit control by 32 weeks. However, 63% of the patients required dose modification, due largely to nausea/vomiting and diarrhea.

“Randomized trials of new agents in comparison to reference standards are necessary to con- firm their value for patients with PV and ET. Correlative studies exploring molecular and metabolic changes may help to understand treatment potential to modify the course of disease,” explained the researchers.

“Continued high-impact research may soon foster the development of disease-modifying therapies for PV and ET and satisfy this need for the optimal management of patients with these MPNs,” they said.

Researchers are also determining how to best optimize current treatment options, including JAK inhibitors and interferons. According to the authors, there is a lack of evidence on disease course modification associated with frontline JAK inhibitor treatment. To build on this data, studies of combination therapy have been initiated.

For example, a phase 2 study of ruxolitinib in combination with pegylated interferon alfa 2a (PEG-IFN alfa-2a) found the regimen was well tolerated, decreased JAK2 V617F allelic burden and symptoms, and resulted in remission for 10 of the 32 patients with PV deemed “almost entirely” intolerant or refractory to PEG-IFN alfa-2a.


Shallis RM, Podoltsev NA. Emerging agents and regimens for polycythemia vera and essential thrombocythemia. Biomark Res. Published online May 28, 2021. doi:10.1186/s40364-021-00298-5