oa PEGylated interferon alfa-2a induces complete hematologic and molecular responses with low toxicity in essential thrombocythemia

Background: Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN) marked by a risk of thrombotic and hemorrhagic complications, and by a long-term risk of evolution to myelofibrosis (MF), and acute leukemia (AL). Methods: Inclusion criteria: ET diagnosed as per WHO classification 2008, age 18 to 45 year. Exclusion criteria: (hepatic and renal dysfunction, history of psychiatric disorder, in particular depression, autoimmune hepatitis, severe cardiac dysfunction, known hypersensitivity to IFN. Complete hematologic response (CR) as per ELN guidelines and molecular response (MR) was defined as 'complete' when JAK2V617F became undetectable with the technique used (i.e., V617F <1%), 'partial' when >50% decrease of baseline V617F was obtained, and 'minor' when V617F decrease was between 20% and 49%. After inclusion, Pegasys was started subcutaneously at 50 microgram weekly for 4 weeks then 135 microgramg/week from week 5. Results: Baseline characteristics of the patients are age 19-44 years, 16 males and 24 females. Five patients had a history of major thrombotic events. All the patients responded to Pegasys at the 12-month evaluation including 35 hematologic CRs (94.6%), and 5 PRs (5.4%). Cumulative incidences of hematologic CRs and PRs showed that 100% of responses were achieved within 12 months. After the first year, V617F continued to decrease without evidence of plateau, the proportion of mutant JAK2 being always similar or lower in the last sample compared with the previous one. None of the responding patients experienced an increase of V617F during follow-up. Median V617F was 58% at 12 months (P <0.001). Hematologic response was achieved in all patients within 2 months and were sustained beyond the first year. Toxicities included musculoskeletal pain in 6 patients, skin toxicity in 4, and GI symptoms in 2, none of the toxicity exceeds WHO Grade 2. Conclusion: PEGylated interferon alfa-2a is an effective and promising treatment for ET reducing the vascular risk and preventing evolution to MF, MDS, and AL. With low toxicity profiles and good hematological and molecular responses, percentage of V617F appears to be a good tool to monitor minimal residual disease and to evaluate treatment efficacy. However, further studies are needed to confirm these results.