P159 Use of Besremi® (pegylated interferon-alfa-2b) in the treatment of cutaneous T-cell lymphoma

Abstract Interferon-alfa has been used to treat mycosis fungoides (MM) and Sézary syndrome (SS) since the 1980s. Type 1 interferons (IFN-alfa and IFN-beta) have antiviral, antitumour, immunomodulatory and antiproliferative properties. The initial marketed product, IFN-alfa-2b (Intron®), was licensed and approved for the treatment of cutaneous T-cell lymphoma in Europe and the USA. Due to the supplier’s financial considerations, Intron® was withdrawn from the market; patients were moved onto IFN-alfa-2a (Roferon®). Roferon was subsequently withdrawn and patients switched to pegylated IFN-alfa-2a (Pegasys®). Peg-IFN-alfa-2a is recommended in the 2023 European Organisation for Research and Treatment of Cancer guidelines for the treatment of MF/SS. Pegasys has the benefit of once-weekly dosing (compared with three times per week for nonpegylated IFNs) and demonstrates similar efficacy. Due to manufacturing issues, there is currently an international shortage of Pegasys. We report our response to this including use of a novel alternative IFN. From our hospital pharmacy records, we identified 21 patients taking Pegasys when forthcoming shortages were announced. Initially, the frequency of administration was reduced from weekly to fortnightly. Initiation of new patients was paused and alternative treatment options considered. Ropeginterferon-alfa-2b (Besremi®), a newer pegylated interferon with similar pharmacokinetics to Pegasys, was identified as the only interferon-alfa product available in England. Besremi is licensed and commissioned in England to treat myeloproliferative neoplasms. It is administered subcutaneously once per fortnight using a prefilled, reusable pen. Besremi 250 μg is therapeutically equivalent to Pegasys 180 μg, and has a National Health Service list price 2.8 times that of Pegasys. Of our 21 patients taking Pegasys, 12 had stage 1B disease, four stage 2B, two stage 3A and two stage 3B, and one had cutaneous lymphoid hyperplasia. All 21 patients initially dose reduced to fortnightly administration; 9 reported a deterioration in their skin. Six (to date) have subsequently switched to Besremi, with seven further switches pending. Four patients moved from Pegasys directly to other therapies due to disease progression or lack of control (two brentuximab, one bexarotene and one total skin electron beam). Four patients have died: two from unrelated causes and two of disease. To date, six patients have been taking Besremi for 6–8 weeks. Early observations indicate that Besremi is at least as effective as Pegasys, with reversal of disease deterioration triggered by dose reduction of Pegasys. Three patients report their skin is stable, and two report an improvement in skin and mood on Besremi. One patient developed a serious adverse event, 5 days after administration of the first dose of Besremi. Symptoms included fever, shortness of breath, cough, skin rash and palpitations, requiring inpatient admission. She has tolerated subsequent doses well, suggesting that this event was unrelated. However, we highlight that palpitations are reported as a common side-effect of Besremi in the product literature. We report ongoing results from the use of Besremi in MF/SS, discussing dosing, efficacy, safety and monitoring.