Real-World Experience of Ropeginterferon in Myeloproliferative Neoplasm Patients

INTRODUCTION: Ropeginterferon alfa-2b njft (Ropeg) is a novel mono-pegylated alfa interferon that was recently approved for the first-line treatment of polycythemia vera (PV). In the phase 3 PROUD-PV/CONTINUATION studies ropeg was efficacious and safe. However, little is known about this agent in real-world practice. We present our experience with myeloproliferative neoplasm (MPN) patients treated with ropeg at our institution.

METHODS: We identified patients who had received prior authorization for ropeg in the Massachusetts General Brigham (MGB) specialty pharmacy. We then collected clinical data and assessed the safety and preliminary efficacy of ropeg in 12 MPN patients treated across the MGB institute.

RESULTS: A total of 12 MPN patients were included in this series, including 11 PV patients and 1 essential thrombocythemia (ET) patient. Median age at ropeg initiation was 53 years (range 31-69), and 67% of patients were male. Of the 11 PV patients, 8 were considered high-risk for PV by National Comprehensive Cancer Network (NCCN) Guidelines, and 3 were considered low-risk. The one ET patient was a low-risk patient by Revised International Prognostic Score of Thrombosis (R-IPSET). Indications for starting therapy included need for cytoreduction due to high-risk status (N=8, including 4 patients who had prior thrombosis); extreme thrombocytosis or worsening platelets and white blood cell (WBC) counts with phlebotomy (N=2), symptoms (N=2), and patient desire to prevent disease progression (N=1). Five patients required phlebotomy within 1 month of starting ropeg.

Five patients were transitioned from a prior therapy, including 3 patients from hydroxyurea, 1 from peginterferon alfa-2a, and 1 from ruxolitinib. In 2 patients transitioning from hydroxyurea, ropeg was started at 50 mcg and the hydroxyurea was tapered off after 11 and 26 days (data not available for the third patient). In the 1 patient transitioning from peginterferon alfa-2a 180 mcg, peginterferon alfa-2a was stopped and ropeg was started at 300 mcg, and then increased by 100 mcg every 2 weeks to a maximum dose of 500 mcg. In the 1 patient transitioning from ruxolitinib, ropeg was started at 100 mcg and ruxolitinib was tapered off after 50 days. All patients tolerated the transition well without any significant cytopenias or need to hold the ropeg. Patients who were not on prior therapy were started on a dose of 100 mcg. All patients except for the patient previously on peginterferon alfa-2a were instructed to increase their dose by 50 mcg every 2 weeks to a maximum dose of 500 mcg per the Food and Drug Administration (FDA) label.

Ropeg was overall well-tolerated in all patients. Two patients had grade 1 increases in liver function tests (LFTs), 1 patient had minor injection site reactions, and 2 patients had malaise which was mild in severity. LFTs resolved after alcohocl cessation in 1 patient, and after dose reduction of ropeg in another; no other dose reductions of ropeg occurred. At time of analysis, the median time on ropeg was 99 days, and the median dose was 350 mcg. Four patients have reached the maximum dose of ropeg at 500 mcg. Four patients required an additional phlebotomy session after starting ropeg.

Follow-up complete blood cell counts (CBC) were obtained at a median of 62 days after ropeg initiation. We found significant decreases in WBC counts compared to baseline (p<0.01), but no significant decreases in hematocrit or platelet counts. At a median follow-up time of 99 days, no patient has yet obtained a complete hematologic response.

CONCLUSIONS: Overall, we found that ropeg is remarkably well-tolerated with improvements seen in hematologic parameters. However, responses are slow, especially with the need for gradual dose up titration, which is consistent with published data. More mature data will be presented at the time of the meeting. Our experience is informative as real-world practices with ropeg can differ significantly from that seen in clinical trials.

Hobbs:Pharmaxis: Other: Advisor or review panel participant; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Advisor or review panel participant; Pfizer: Other: Advisor or review panel participant; Constellation: Membership on an entity's Board of Directors or advisory committees, Other: Advisor or review panel participant; PI, Research Funding; Abbvie Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Other: Advisor or review panel participant; Incyte: Other: Advisor or review panel participant; PI, Research Funding; Keros: Other: Advisor or review panel participant; Bristol Myers Squibb Co./Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Advisor or review panel participant; Bayer: Research Funding; Merck: Research Funding.