Phenotypic and functional analysis of peripheral blood lymphocytes during interferon-alpha 2b therapy in multiple myeloma patients with low tumor mass

Background. IFN-α has recently been shown to prolong the remission phase in MM patients with low tumor mass. So far, it is not known whether IFN-α exerts its effect directly on the myeloma cells or is mediated by modulation of the host response. Methods. The immune status of 12 multiple myeloma patients with low tumor mass (10 in remission phase, 2 with stage IA disease) was investigated by phenotypic and functional analyses before, after 3, and after 6 months of recombinant interferon-alpha2b (IFN-α) therapy. Results. Phenotyping of peripheral blood lymphocytes (PBL) revealed a significant decrease of HLA-DR+ (P = 0.01) and CD20+ (P = 0.04) cells after 6 months of therapy. Two-color phenotyping of purified T cell populations (PBT) showed a significant increase of CD4+ CD11b^+ cells (P = 0.01) after 6 months of therapy. Functional analyses were carried out on PBL (NK cell-mediated cytotoxicity) and PBT (alloreactive cytotoxicity, CTL; IL2-induced cytotoxicity, LAK activity). NK and CTL activities were poorly influenced by IFN-α treatment, whereas LAK activity showed a significant increase (P = 0.007). Any significant association between these immunological changes and the disease status was questioned by the lack of differences between MM in relapse and MM with stable disease as the sixth month of IFN-α therapy. Conclusions. i) IFN-α in MM with low tumor mass may exert its therapeutic activity by directly acting on the tumor cells; ii) the parameters which have been used in this study are not appropriate to monitor the immunological effects (if any) of IFN-α therapy.