Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial

Abstract

BackgroundThe durability of responses and long-term safety of pegylated interferon alpha-2a (PEG-IFN-a-2a) in patients with polycythemia vera and essential thrombocythemia have not been reported. Here, we present long-term efficacy and safety data from a single-center, prospective, phase 2 study, after 7 years of follow-up.MethodsPatients older than 18 years who were diagnosed with essential thrombocythemia or polycythemia vera per 2001 World Health Organization criteria were eligble to enroll.Responses were assessed every 3–6 months: Data were analyzed using descriptive statistics. The rate of leukemia transformation was compared with age- and gender-matched patients who were not treated with PEG-IFN-α-2a.FindingsPEG-IFN-α-2a induced hematologic (80%) and molecular responses (63%) in 83 patients with essential thrombocythemia (n=40) and polycythemia vera (n=43), with median durations of 66 and 53 months, respectively. Thirty-nine percent of hematologic responders and 71% of molecular responders (JAK2V617F+) have maintained some response during follow-up: 48% maintained their best molecular response, including 9 of 10 patients with a complete molecular response. The incidence of major venous-thrombotic events during the study was 1.22/person-year. Overall, 22% of patients discontinued therapy due to treatment-related toxicity. While toxicity rates decreased over time, 5 patients experienced treatment-limiting G3/4 toxicities after 60 months on therapy. Rates of transformation to MF/AML were similar between patients treated with PEG-IFN-a-2a and those from a historical control series.InterpretationPEG-IFN-α-2a can induce durable hematologic and molecular remissions in patients with essential thrombocythemia and polycythemia vera. We suggest a starting dose of 45 mcg/week, and its combination with other drugs should be explored further in clinical trials.

JAK2 inhibitors for myeloproliferative neoplasms: what is next?

“…116 Both pegylated interferon alfa-2a (administered once per week) and ropeginterferon alfa-2b (administered once every 2 weeks) are associated with high rates of hematologic and molecular response in patients with PV and ET [117][118][119] ; however, at least in the case of pegylated interferon alfa-2a, discontinuation rates as a result of toxicity can still be substantial. 120 In MF, the role of interferon monotherapy is essentially limited to some patients with early disease. 121,122 A 90% ORR to the combination of interferon alfa-2 and ruxolitinib was reported in a small trial (n 5 30; 20 PV, 7 PMF, 3 post-PV MF; 27 previously treated with interferon alfa-2), 123 with marked improvements in symptoms, palpable splenomegaly, and hematocrit control without phlebotomy, suggesting that such combinatorial approaches should be pursued, particularly in light of renewed interest in interferon after the demonstration of noninferiority of ropeginterferon alfa-2b to HU in patients with PV.…”

Developmental Therapeutics in Myeloproliferative Neoplasms

“…Results after a median of 7 years (82.5 months) of follow-up of a phase II study of pegylated interferon alfa-2a conducted at the MD Anderson Cancer Center were recently presented. 25 Patients (43 PV, 40 ET) could be newly diagnosed or previously treated. The overall median exposure to therapy was 87 months.…”

“…Even among patients in complete hematologic remission (CHR), vascular adverse events (AEs) and disease transformation occurred in 5 patients each. 25 …”

Patients with essential thrombocytosis during pregnancy: Challenges and therapeutic dilemmas

“…In addition, another successful high-risk pregnancy has been reported under treatment with Peg-IFN combined with ASA and LMWH. This was the only successful pregnancy, which produced a healthy baby since she has a history of miscarriages and pregnancy complications (stillbirth, hypertension, neonatal death) in the past [58,59].…”