Pegylated Interferons Have Promise but Also Unmet Potential in MPNs

Pegylated interferons are a meaningful therapeutic option for the treatment of myeloproliferative neoplasms (MPNs), but a new review article says more research is needed to better understand the ideal usage of the therapy.

The report was published in Therapeutic Advances in Hematology.

Study investigators said several interferon products are currently available to treat patients with MPNs, but they said the short half-life of interferons and the risk of (AEs) effects have limited their usage. Pegylation can help overcome those issues, they said.

“Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule,” the authors wrote.

More research is needed to better understand when and in whom pegylate interferon therapy is most effective | Image Credit: Iamnee - stock.adobe.com

They said current National Comprehensive Cancer Network guidelines call for pegylated interferons to be used for polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Currently, there are 2 pegylated interferons available for patients with MPNs, they said: peginterferon alfa-2a (Pegasys; pharma&) and ropeginterferon alfa-2b-njft (BESREMi; PharmaEssentia). Both medications are recommended as cytoreductive therapies for PV, the investigators said.

“In high-risk ET and low-risk PMF, peginterferon alfa-2a is recommended as a cytoreductive therapy option,” they said.

Yet, the investigators said the promising safety and efficacy profiles of pegylated interferons has not reversed the pattern of relatively low real-world usage rates for interferons. One reason, they said, is patient concern about the risks of AEs. They noted that in a chart review of 1400 patients with PV from 42 medical centers, the rates of cytoreductive therapy in high-risk patients varied widely, from 10% to 100%. When cytoreductive therapy was given, hydroxyurea was used in almost three-quarters of cases; only 2% of patients were treated with pegylated interferons. However, they also noted that pegylated interferons are becoming more common in younger patients who have MPNs, “given [the therapies’] lack of genotoxicity and carcinogenenicity.”

Still, the investigators said the fears over AEs with interferons are worth considering, particularly since patients with MPNs often require long-term treatment.

“A 7-year (median) follow-up of a phase 2 study in patients with PV and ET who received peginterferon alfa-2a (90-450 mcg/week subcutaneously) showed that, although rates of AEs decreased over time, they did not disappear entirely,” the authors noted.

Fatigue, anemia, neutropenia, and depression were all noted in certain patients years after the initiation of therapy.

“Two or more years from the start of interferon therapy, new grade 3 and 4 toxicities unrelated to dose occurred in 10% to 17% of patients per year,” the authors added.

One area of ongoing research is biomarkers, with the hope that certain markers might help identify patients most likely to benefit from interferon therapy. However, the authors said existing studies on biomarkers have been limited in number and thus further research is needed.

Another avenue of inquiry is the role interferons might play in combination therapies, the authors said. For instance, at least 2 studies looked at combining interferons with ruxolitinib (Jakafi; Incyte) in patients with MF and PV. Both studies suggested the combination held promise.

“This therapeutic approach is worthy of prospective randomized trials with single-agent ruxolitinib as the control arm,” they wrote.

In their conclusion, the investigators said interferons carry disease-modifying potential that sets them apart from other available treatments. However, they said more research is needed to better understand when and in which patients the therapy is most effective, and to determine whether it might be possible to discontinue treatment if minimal residual disease status is achieved.

“Pegylated interferons represent an important therapeutic option, and future work will further refine therapeutic approaches with a goal of achieving true disease modification for patients with MPNs,” they concluded.

Reference

Vachhani P, Mascarenhas J, Bose P, et al. Interferons in the treatment of myeloproliferative neoplasms. Ther Adv Hematol. 2024;15:20406207241229588. doi:10.1177/20406207241229588