Interferon gamma as immunomodulator in a patient with multiple myeloma

We describe here a patient with multiple myeloma, who, while in remission after chemotherapy, received 100 micrograms of rIFN-gamma (Imukin, Boehringer, Ingelheim) subcutaneously 3 times a week for 4 weeks as supportive therapy before autologous peripheral blood stem cell transplantation (PBSCT). The patient was monitored for serum IFN, TNF, IL-2 activities and for the ability of peripheral blood leukocytes (PBL) to produce IFN-alpha/beta, IFN-gamma, IL-2 and TNF-alpha after in vitro induction. Changes in the percent of plasma cells in the bone marrow, in the total and differential white blood cell counts, in T cell subsets and NK cells were also monitored. IFN-gamma yielded no clinical antitumor activity. The number of bone marrow plasma cells increased, however, the percentage of blood and bone marrow NK cells and the CD4/CD8 T cell subset ratio decreased. Monitoring the cytokine production ability of PBL during IFN-gamma therapy revealed an increase in IL-2, IFN-gamma and TNF-alpha titers produced upon in vitro induction after 2 weeks of treatment (6 injections of rIFN-gamma). However, after 9 injections there was a significant decrease in IFN-gamma and IL-2 production in the PBL, and at the end of therapy (12 injections) the decrease not only in IL-2 and in IFN-gamma but also in IFN-alpha production was observed. In contrast to these changes, TNF production was strongly enhanced and reached the level observed before the therapy. These data suggest that the schedule of IFN-gamma therapy in multiple myeloma should perhaps be adapted to become more effective, taking advantage from the immunomodulating activity of IFN-gamma.