NCCN Guidelines Add Ropeginterferon Alfa for First-Line Polycythemia Vera

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The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology have been updated to include ropeginterferon alfa-2b-njft (Besremi) as a preferred option for first-line cytoreductive therapy in patients with symptomatic, low-risk polycythemia vera (PV).¹

“The recent update to the NCCN Guidelines reflects the ongoing shift in PV care towards earlier intervention, focusing on long-term patient health,” said Rami Komrokji, MD, vice chair of the malignant hematology department and head of the leukemia and myelodysplastic syndrome section at Moffitt Cancer Center, in a press release.

Ropeginterferon alfa is the only preferred therapy for symptomatic high-risk and low-risk PV. The monopegylated, long-acting interferon was given an orphan drug designation and approved by the FDA in 2021.

Five-Year Follow-Up Study of Ropeginterferon Alfa in Polycythemia Vera

Findings from 5-year follow-up the phase 3 PROUD-PV (NCT01949805) and phase 3b CONTINUATION-PV (NCT02218047) trials on patients with PV treated with ropeginterferon alfa were published in 2022. They showed that the complete hematologic response (CHR) rate was 55.8% in the ropeginterferon alfa arm vs 44% in the control arm.² The molecular response rate at 5 years was also higher in the ropeginterferon alfa arm at 69.1% vs 21.6% in the control arm (RR, 3.04; 95% CI, 1.96-4.71; P <.0001).

Regarding safety, the incidence of adverse events (AEs) was balanced between the arms. In the ropeginterferon alfa arm, the most common AEs occurring in 10% or more of patients were thrombocytopenia, anemia, leukopenia, elevated hepatic enzymes, arthralgia, fatigue, headache, dizziness, splenomegaly, pyrexia, and back pain. In the control arm, the most common AEs were thrombocytopenia, anemia, leukopenia, fatigue, headache, nausea, diarrhea, influenza, and nasopharyngitis. Most AEs were grade 1 or 2.

Importantly, the findings from this 5-year follow-up suggested that treatment discontinuation without disease progression could be considered, which is not currently possible with other available therapies for PV.

Dosing Strategies for Ropeginterferon Alfa in Polcythemia Vera

Ropeginterferon alfa is administered every 2 to 4 weeks at a starting dose of 100 µg or 50 µg for patients receiving hydroxyurea. Intrapatient dose titrations are given in 50 µg increments up to 500 µg.³ This dosing schema allows for more flexible administration that can meet a patient’s needs.

Findings from a 2023 study (NCT05485948) investigated an alternate dosing schedule of a higher starting dose and quicker intrapatient dose titrations in patients who were resistant or intolerant to hydroxyurea. The study found that this dosing schema demonstrated a CHR at week 24 of 61.2% vs 43.1% at 12 months with the approved dosing schedule.

Ropeginterferon alfa appeared to be tolerated in this regimen, and the most common AEs were grade 1 or 2 alanine aminotransferase and aspartate aminotransferase increases.

REFERENCES:

1. PharmaEssentia’s BESREMi (ropeginterferon alfa-2b-njft) now recommended as a preferred first-line cytoreductive therapy for polycythemia vera in updated NCCN clinical practice guidelines in oncology (NCCN guidelines). News release. PharmaEssentia USA Corporation. February 27, 2024. Accessed February 28, 2024. http://tinyurl.com/n6vwjzrn

2. Kiladjian JJ, Klade C, Georgiev P, et al. Long-term outcomes of polycythemia vera patients treated with ropeginterferon Alfa-2b. Leukemia. 2022;36(5):1408-1411. doi:10.1038/s41375-022-01528-x

3. Jin J, Zhang L, Qin A, et al. A new dosing regimen of ropeginterferon alfa-2b is highly effective and tolerable: findings from a phase 2 study in Chinese patients with polycythemia vera. Exp Hematol Oncol. 2023;12(1):55. Published 2023 Jun 21. doi:10.1186/s40164-023-00415-0