NCCN Recommends Ropeginterferon Alfa-2b in Clinical Practice Guidelines Update

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology has been revised to include ropeginterferon alfa-2b-njft (Besremi) as a recommended treatment option for adult patients with polycythemia vera, according to a news release from the developer of the agent, PharmaEssentia.¹

“Importantly, the NCCN Guidelines update includes mention of [ropeginterferon alfa-2b] in multiple settings, and in particular, as the only systemic option for low-risk patients with polycythemia vera, which signals a shift toward more proactive treatment earlier in the disease journey,” Ruben Mesa, MD, FACP, executive director of the UT Health San Antonio MD Anderson Cancer Center, stated in a news release. “Now, treating physicians can leverage these expert guidelines to gain greater familiarity with [ropeginterferon alfa-2b] in the real-world setting and understand its broad utility for patient care in a variety of treatment settings.”

On November 12, 2021, the FDA approved ropeginterferon alfa-2b as a treatment for patients with polycythemia vera based on findings from the PEGINVERA (NCT01193699), PROUD-PV, and CONTINUATION-PV trials.

In PEGINVERA, 61% of patients achieved a complete hematological response after 7.5 years of treatment with ropeginterferon alfa-2b-njft, which was defined as hematocrit of less than 45% without phlebotomy for at least 2 months since last phlebotomy, platelet counts of 400 x 10⁹/L or less, leukocytes of 10 x 10⁹/L or less, and normal spleen size (longitudinal diameter ≤12 cm for females and ≤ 13 cm for males).²

Additionally, most patients (80%) developed a hematological response with the agent according to objective laboratory parameters predominantly, with normal spleen size and thrombosis.

In PEGINVERA, the most common adverse effects occurring in at least 40% of patients were influenza-like illness (59%), arthralgia (47%), fatigue (47%), pruritis (45%), nasopharyngitis (43%), and musculoskeletal pain (41%). Serious adverse reactions occurring in at least 4% of patients were urinary tract infection (8%), transient ischemic attack (6%), and depression (4%).

The PROUD-PV and CONTINUATION-PV trials enrolled patients who were at least 18 years of age with a diagnosis of early-stage polycythemia vera, according to the World Health Organization 2008 criteria.³

In PROUD-PV, patients were randomized 1:1 to a 100-μg biweekly starting dose of subcutaneous ropeginterferon alfa-2b or a 500-mg daily starting dose of oral hydroxyurea. At 1 year, patients were allowed to enroll to the extension portion of the study, CONTINUATION-PV.

The primary end point of PROUD-PV was noninferiority of ropeginterferon alfa-2b vs hydroxyurea with regard to complete hematological response with normal spleen size at 1 year. The coprimary end points of CONTINUATION-PV were complete hematological response with normalization of spleen size and improved disease burden based on splenomegaly, microvascular disturbances, pruritus, and headache.

The median follow-up was 182.1 weeks in the ropeginterferon alfa-2b arm and 164.5 weeks in the hydroxyurea arm.

In PROUD-PV, 21% (n = 26) of patients in the ropeginterferon alfa-2b arm (n = 122) and 28% (n = 34) of those in the hydroxyurea arm (n = 123) met the composite primary end point of complete hematological response. Moreover, at 36 months, improved disease burden was achieved in 53% (n = 50) of patients who received ropeginterferon alfa-2b vs 38% (n = 28) of those who received hydroxyurea (n = 74; P = .044).

Further results from PROUD-PV showed that the 1-year complete hematological response rate without the spleen criteria was 43% (n = 53/123) in the ropeginterferon alfa-2b arm vs 46% (n = 57/125) in the hydroxyurea arm (P = .63). At 36 months in CONTINUATION-PV, these rates were 71% (n = 67/95) vs 51% (n = 38/74), respectively (P = .012).

“Our goal with [ropeginterferon alfa-2b] has been to offer a compelling therapeutic alternative to conventional treatment options that can enable physicians to gain durable control over the disease beyond the symptoms and help more patients reach their long-term health goals,” Raymond Urbanski, MD, PhD, US Head of Clinical Development and Medical Affairs, said in the news release. “The NCCN Guidelines update just 3 months following our approval illustrates the community’s recognition of the strong potential of [ropeginterferon alfa-2b] in polycythemia care.”

Ropeginterferon alfa-2b is approved with a boxed warning for risk of aggravation of neuropsychiatric, autoimmune, ischemic, and infectious disorders.

References

1. NCCN clinical practice guidelines in oncology update recommends besremi (ropeginterferon alfa-2b-njft) for the treatment of polycythemia vera. News release. PharmaEssentia. March 2, 2022. Accessed March 2, 2022. https://bit.ly/3HwMNr7
2. Besremi. Prescribing information. PharmaEssentia; 2021. Accessed March 2, 2022. https://bit.ly/3IFyj9J
3. Gisslinger H, Klade C, Georgiev P, et al. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020;7(3):e196-e208. doi:10.1016/S2352-3026(19)30236-4