Anti-Interferon Alpha Antibodies in Patients with High-Risk BCR/ABL-Negative Myeloproliferative Neoplasms Treated with Recombinant Human Interferon-α

BACKGROUND: The objective of this study was to characterize the incidence and impact of immunogenicity to interferon-α (IFN-α-2a, IFN-α-2b, and Peg-IFN-α-2a) over a period of 12 months in patients with BCR/ABL-negative myeloproliferative neoplasms (MPNs). MATERIAL/METHODS: A total of 131 patients from an observational prospective cohort were selected. Antidrug antibodies, in serial serum samples obtained monthly after initiation of therapy, were measured by ELISA and WISH/VSV CPE assays. The association between antidrug antibodies and treatment response and adverse effects was evaluated. RESULTS: Among patients who completed 12 months of follow-up, binding antibodies (BAbs) were detected in 53% of those receiving IFN-α (69 of 131) and neutralizing antibodies (NAbs) were detected in 19% (25 of 131). NAbs-positivity was correlated with poorer clinical response, and Bab-positivity was associated with more adverse events. Almost all BAbs and NAbs appeared within 8 months after treatment began (≥95%). Complete remission (CR) rate was 62% for patients who were BAbs-positive and 69% for patients who were BAbs-negative; however, the CR rate of patients with NAbs(+) (24%) was obviously lower than in patients with NAbs(−) (75%). Patients with BAbs(+) had more immune adverse effects (including fever, myalgia, skin reaction, and stomatitis) than BAbs(−) patients, and NAbs to IFN-α had no obvious influence on the adverse effects rate. CONCLUSIONS: The development of BAbs and NAbs can adversely affect IFN-α treatment in patients with MPN.