PVN1: A Phase 2 Study of Pegylated Interferon-α2a in Polycythemia Vera (PV) by the “PV-Nord” Group. Preliminary Report of Efficacy and Safety.

Background: Interferon-α (IFN) can control erythrocytosis in about 75% of PV patients and may even induce cytogenetic remission while avoiding the leukemogenic potential of myelosuppressive drugs. However, 20–25% of patients discontinue therapy due to side effects. Pegylated-IFN (peg-IFN) α2b, usually better tolerated than standard IFN, has shown similar efficacy but no advantage in terms of tolerance in PV (ASH 2004, abstracts 1517 & 1518). The use of peg-IFN-α2a has not been reported in PV to our knowledge. The French “PV-Nord” group performed an open label phase II study of peg-IFN-α2a (Pegasys®, Roche Laboratories) in PV patients.

Study design: Inclusion criteria were: PV diagnosed according to PVSG criteria, aged 18 to 65, previously untreated, or only phlebotomized, or with cytoreductive treatment for less than 2 years. Complete response (CR) was defined by Ht lower than 45% in male and 42% in female without phlebotomy for more than 3 months, absence of splenomegaly and normal WBC and platelet counts. Partial response was defined by Ht as above but persistent splenomegaly or elevated platelet count, or > 50% decrease in phlebotomies. Failure was defined by persistent phlebotomies to maintain Ht in the target range. Primary objective was determination of response rate; secondary objectives were evaluation of toxicity and evolution of molecular markers (i.e. detection of JAK2 mutation and PRV-1 expression) on peg-IFN.

Results: Between September 04 and August 05, the 37 initially planned patients were included. 20 of them had a follow-up greater than 6 months and were evaluable for response: M/F ratio 7/13, median age 49 years (range 22–65). Median time from diagnosis to inclusion in the 20 patients was 6 months (range 1–65). 14 patients (70%) were either untreated or only phlebotomized before inclusion and 6 (30%) had previously received hydroxyurea. 25% of patients had a history of thrombosis. Median Ht was 56% in males (range 46–66) and 45% in females (range 40–60). Median WBC and platelet counts were 8.10⁹/l (range 3–23) and 571.10⁹/l (range 120–1478), respectively. 30% of patients had splenomegaly. After 3 months, all patients were responders, with 15 CR (75%) and 5 PR (25%). At 6 months, 95% of patients were responders with 16 CR (80%) and 3 PR (15%) (persistent splenomegaly in 2, elevated platelets in 1). Only grade 1 and 2 toxicities were reported. Most frequent toxicities were fatigue (n=6), muscle and joint pain (n=6) and disturbances of gastro-intestinal tract (n=3). Fever and depression (grade1 for both) were observed in 3 and 2 patients respectively. Only one patient discontinued treatment due to repeated grade 2 thrombocytopenia.

Conclusion: This is the first report of a phase II trial using peg-IFN-α2a in PV. The 95% response rate after 6 months of treatment and only 5% treatment withdrawal due to side effects suggest that peg-IFN-α2a is at least as effective and as well tolerated as both standard IFN and peg-IFN-α2b in PV. Updated results will be presented.