Clinical experience of antibodies to interferon-alpha during treatment of chronic myeloid leukemia

Interferon-alpha (IFN-alpha) remains the only viable alternative to bone marrow transplantation for patients with chronic myeloid leukemia (CML) and is the treatment of choice in many circumstances. IFN-alpha can induce hematologic remissions in most patients with CML and suppresses the Philadelphia chromosome-positive cell clone in 30%-40% of hematologically responsive patients. IFN-alpha can also prolong the length of the chronic disease phase and survival time in patients who achieve a karyotypic response. A third of patients, however, never respond to IFN-alpha, and a proportion of the initial responders will later become resistant. It has been suggested that the induction of anti-IFN-alpha antibodies might be one of the reasons for resistance to IFN-alpha. It is difficult to evaluate the factors that influence antibody induction and the effects of these antibodies on clinical results. The source of IFN-alpha product, trial design, and differences in the sensitivity of the assays used to measure antibodies are all factors that need to be considered.