LOW-DOSE RECOMBINANT INTERLEUKIN-2 THERAPY IN ADVANCED MULTIPLE-MYELOMA

In vitro data have demonstrated autologous T-lymphocytes with anti-tum our activity in multiple myeloma (MM). Therefore a phase I/II trial wa s conducted to study the feasibility, the effect on several immunologi cal parameters, and the tumour response induction of low-dose recombin ant interleukin-2 (rIL-2) in MM patients. 18 MM patients of advanced s tages in progress, who had failed on standard chemotherapy received 9 x 10(6)IU/m(2) rIL-2 twice daily on days 1 and 2 and 0.9 x 10(6)IU/m(2 ) twice daily for 5 subsequent days per week subcutaneously from days 3 to 56 (repeated every 12 weeks until progression). Patients were tre ated for between 8 and 1086+d (mean 241 d) without serious side-effect s. 6/17 patients experienced tumour response (2/17 objective tumour ma ss reduction, 4/17 long-lasting stable disease following tumour progre ssion before initiation of rIL-2 treatment). During therapy the number of eosinophils increased 15-fold, CD4(+) T lymphocytes were activated as demonstrated by enhanced CD25 antigen expression, and CD56(+) NK c ells expanded in the peripheral blood. Furthermore, a diminished pre-t reatment ratio of CD4(+)/CD8(+) lymphocytes was normalized during rIL- 2 treatment. NK cell activity and lymphokine activated killer (LAK) ce ll activity was significantly enhanced. Endogenous IL-2 production and elevated soluble IL-2 receptor serum concentrations were induced. Low -dose rIL-2 can stimulate immune enhancement in MM despite the charact eristic tumour-induced immunodeficiency. The treatment has proven thou gh limited efficacy in advanced MM. Because most of the responders exp erienced termination of tumour progression rather than tumour regressi on, rIL2 maintenance of chemotherapy-induced remissions should be inve stigated.