Long-Term Id Vaccination Combined with IL-12 or IL-12 and GM-CSF in Early Stage Multiple Myeloma Patients.

The idiotypic structures expressed on the myeloma Ig protein may serve as tumor specific antigens and can be used as target structures for Id (Id) vaccination. In this study, 28 patients with IgG myeloma stage I-II were repeatedly immunized intracutaneously during a 110 week period with the autologous M-protein, either in combination with interleukin-12 (IL-12) (n=15), or with IL-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) (n=13). An Id-specific T cell response, as assessed by [³H]-thymidine incorporation, ELISPOT assay and delayed type hypersensitivity (DTH) reaction and strictly defined by 3 specified criteria, developed in 4/15 patients (27%) in the IL-12 group and 11/13 patients (85%) in the GM-CSF/IL-12 group (p=0.003). Three of 15 patients (20%) showed a gradually increasing Id-specific T cell response during the study whereas 10/15 patients (67%) showed an initial response which then disappeared rapidly; the latter pattern was frequently associated with subsequent progressive disease. In two patients (both in the IL-12 group) a reduction of the M-protein concentration by > 50% and >25%, respectively, was observed 18 and 21 months after the last immunization. These results indicate that Id immunization of myeloma patients using IL-12 and GM-CSF may more frequently induce a specific T cell response than with IL-12 alone, but also that repeated immunizations may result in a non-reversible state of tolerogenic T cells.