Neutralizing anti-interferon-α antibodies and response to treatment in patients with Ph+ chronic myeloid leukaemia sequentially treated with recombinant (α2a) and lymphoblastoid interferon-α

Abstract

Neutralizing anti-IFNα antibodies (nIFNα Abs) occur in a significant proportion of patients with hairy cell leukaemia, hepatitis or solid tumours treated with recombinant IFNα (IFNα2a or IFNα2b), but information on their incidence in chronic myeloid leukaemia (CML) is scanty and their clinical relevance is not yet completely defined. By using an IFNα antiviral neutralization bioassay, the frequency of nIFNα2a Abs was evaluated in 67 Ph+ CML patients during IFNα2a therapy at doses ranging from 6 to 9 MU/d. 15 patients (22%) developed nIFNα2a Abs (titre ranging from 1:40 to 1:20480) and 11/15 (73%) were haematologically and/or karyotypically unresponsive to treatment. 52 patients did not develop antibodies and 11 of them (21%) were unresponsive. The negative relationship between the positivity for nIFNα2a Abs and the response to treatment was highly significant (P = 0.0001). In nine nIFNα2a Abs positive patients, treatment was changed from recombinant IFNα2a to lymphoblastoid IFNα(IFNα-ly), at the same dose and schedule. After 9 months of IFNα-ly treatment a haematological response was achieved in 4/7 cases who were non-responsive to prior IFNα2a therapy and was maintained in the other two patients previously responsive to IFNα2a. However, no karyotypic response was observed. This data shows that a significant proportion of Ph+ CML patients receiving treatment with IFNα2a can develop neutralizing antibodies and that these antibodies are associated with a loss of IFNα2a efficacy. Changing the patients to treatment with lymphoblastoid IFNα may restore haematological response but it is not likely to induce a karyotypic response.