Retrospective real-world analysis of ropeginterferon ALFA-2B use in patients with polycythemia vera and essential thrombocythemia: Practice patterns, tolerance, and outcomes

Abstract Introduction: In November 2021 ropeginterferon alpha-2B (ropeg) was approved by the FDA for front-line management of PV regardless of thrombotic risk based on the LOW-PV and PROUD/CONTINUATION-PV trials that demonstrated high rates of hematologic response and consistent reductions in the JAK2 V617F variant allele burden. Despite encouraging efficacy and tolerability, given its limited use, we aimed to characterize real-world experience. Methods: We conducted a retrospective chart review of patients identified through Mass General Brigham (MGB) specialty pharmacy. Data on safety and efficacy were collected. Results: Ninety-seven patients were identified; 12 were excluded due to incomplete records, inadequate follow-up, or not starting the medication. Eighty-five patients were included in the analysis of toxicity and tolerability; 78 were included in the efficacy analysis at 6 months and 63 at 12 months (patients excluded due to not enough time passed or unavailable complete blood count (CBC)). Among the 85 patients, 75 had PV, 9 ET, and 1 MPN unclassified. Mean age was 49 (range 18–76), 47% (n=40) were female, and 85% (n=72) identified as Caucasian. 11% (n=9) had autoimmune conditions, 28% (n=24) had a psychiatric diagnosis, and 52% (n=44) had a co-morbid cardiovascular condition. Among patients with PV, 39 were classified as low-risk and 36 as high-risk. For ET patients, 4 were low-risk, 2 intermediate, and 3 high-risk. Twenty-three patients received prior phlebotomy alone. Fifty patients (59%) received prior cytoreduction. Forty-two percent (n=36/85) received concurrent hydroxyurea (median overlap 11 weeks; range 1–97 weeks) when starting ropeg. The most common starting dose of ropeg was 100 mcg every 2 weeks (73%, n=62; range 50–300 mcg q2 weeks). At the time of data collection, 69% (n=59) of patients remained on therapy with a median treatment duration of 16 months (range 1-42 months). There were 26 discontinuations (30%) due to toxicity (88%), progression to myelofibrosis (8%), or lack of response (4%). Forty-two percent (n=36) of patients reached the maximum dose of 500 mcg q2 weeks; of those, 42% (n=15) subsequently reduced their dose (17%) or dosing frequency (25%). The median final dose was 325 mcg (range 50–500 mcg), with a median dosing interval of 2 weeks (range 2–8 weeks). Sixty-six patients (78%) experienced at least one toxicity; pruritus, transaminitis, and cytopenias were the most common, occurring in 25%, 20%, and 19% of patients, respectively. Of the patients with pre-existing psychiatric comorbidities (n=24), 3 experienced worsening of their anxiety/depression that led to discontinuation of ropeg in 2 patients. One patient without previous history of a psychiatric condition experienced new anxiety that led to discontinuation. Of the 9 patients with pre-existing autoimmune comorbidities, 1 experienced worsening of their thyroid condition that led to discontinuation of ropeg. CHR was evaluated at 6 and 12 months for patients with available CBCs. At 6 months, 44% (n=34/78) achieved CHR; At 12 months, 51% (n=32/63) achieved CHR. Of the 20 patients with molecular testing before and after starting ropeg, 70% (n=14) had a decline in JAK2 VAF. The average reduction in VAF was 1.6%/month. Of the 7 patients that had molecular testing after 12 months on ropeg (range 12-36 months) whose JAK2 VAF decreased, the average decrease was 22.6%. Forty percent (n=8) met European Leukemia Network (ELN) criteria for a partial molecular response with none meeting criteria for complete response. Of note, VAF was not consistently obtained immediately before starting ropeg. Conclusions: We present the latest real-world data on ropeginterferon use confirming its efficacy in achieving CHR and reducing JAK2 allele burden. At 6 months 44% had achieved a CHR. Seventy percent of patients experienced a decline in JAK2 VAF. Ropeginterferon was well tolerated across a wide range of doses, with many patients using a lower or less frequent dosing regimen than the label recommends. In addition, there was a low incidence of psychiatric and autoimmune toxicities.