PB2227 COMPASSIONATE USE OF ROPEGINTERFERON TO TREAT MYELOPROLIFERATIVE NEOPLASMS IN TAIWAN
Authors: C.‐C. Chen, M.‐C. Kuo, Y. ‐.‐J. Su, C.‐E. Huang, C.‐C. Hsu, Y.‐Y. Wu, Y.‐J. Chen, L.‐Y. Shih
Journal: HemaSphere (2019)

Background: There is a high unmet medical need for therapeutic options for patients suffering from myeloproliferative neoplasms (MPN), who have failed or are not eligible to available treatment options. Ropeginterferon‐alfa‐2b (P1101) is a novel, third generation pegylated interferon‐alfa, recently approved by EMA to treat polycythemia vera (PV). Ropeginterferon‐alfa‐2b is also in the late stages of development in several countries for treatment of PV and other MPNs. Aims: Ropeginterferon‐alfa‐2b is a new and attractive treatment option for patients suffering from MPN who have exhausted all therapeutic options and require treatment. The Compassionate Use Program (CUP) was approved and initiated in Taiwan with the purpose of granting access to P1101 to patients with MPN disease with no therapeutic options who are not eligible to enroll in existing clinical trials for their disease. Methods: Patients were identified that had the potential to benefited from P1101 therapy and were eligible according to the protocol. Patients were treated at a starting dose of 250 ug with subsequent dose escalation every 2 weeks over a 6‐week period to 350 ug, 450 ug and 500 ug. Dose adjustments were permitted based on tolerability and efficacy. Results: The CUP currently contains 15 patients from two academic hospitals: 9 with PV, 2 with post‐PV myelofibrosis (MF), two with pre‐fibrotic MF, one with primary MF, and one essential thrombocythemia patient. The driver mutation was JAK2 in 13 patients, CALR in one, and another one was triple negative. Pre‐treatment with hydroxyurea and/or anagrelide was reported in 13 patients. P1101 was given for &gt; 12 weeks to 14 patients (range 4 ‐ 64 weeks). The highest administered dose of P1101 was: 500 ug in 11 patients (time to highest dose – 6 weeks in 9 patients, 10 weeks – in 1 and 20 weeks in another patient); 250 ug, 350 ug and 450 ug in three other patients. The need to decrease or temporarily interrupt P1101 therapy occurred in 4 patients, all due to transaminase(s) elevation. Notably, these events did not require permanent discontinuation of therapy and could be alleviated by appropriate dose modifications. The majority of observed adverse events were of grade 1 and included fatigue, arthralgia, myalgia, chills and dizziness. Grade 2 events included elevation of transaminases (in 3 patients), dizziness, pruritus and lower limbs pain (in 1 patient each). One patient developed elevation of transaminases of grade 3. Normalization of blood parameters within complete hematologic response range was observed in 3 PV and 2 post‐PV MF patients. Two PV patients fulfilled the partial response criteria. In other patients, decrease of platelet count (even in previously treatment‐resistant thrombocytosis) and symptomatic improvement were also observed. No major cardiovascular events were recorded. One pre‐PMF patient transformed into MF (grade 5). No patients progressed to acute myelogenous leukemia (AML) during the observation. Summary/Conclusion: In this cohort of MPN patients, not amenable for established treatment options, P1101 demonstrated good tolerability and substantial efficacy. The dose administration schema with a starting dose of 250 ug and escalation to the highest dose of 500 ug within the first 6‐8 weeks was feasible, tolerated and allowed rapid control of blood parameters. The observed efficacy demonstrate P1101 as a promising treatment option for patients with MPNs with limited or no alternate therapeutic option. These results mandate access to P1101 at earlier stages of disease as recommended by international MPN treatment guidelines.