Low-dose recombinant interleukin-2 therapy in advanced multiple myeloma.
In vitro data have demonstrated autologous T-lymphocytes with anti-tumour activity in multiple myeloma (MM). Therefore a phase I/II trial was conducted to study the feasibility, the effect on several immunological parameters, and the tumour response induction of low-dose recombinant interleukin-2 (rIL-2) in MM patients. 18 MM patients of advanced stages in progress, who had failed on standard chemotherapy received 9 x 10(6) IU/m2 rIL-2 twice daily on days 1 and 2 and 0.9 x 10(6) IU/m2 twice daily for 5 subsequent days per week subcutaneously from days 3 to 56 (repeated every 12 weeks until progression). Patients were treated for between 8 and 1086 + d (mean 241 d) without serious side-effects. 6/17 patients experienced tumour response (2/17 objective tumour mass reduction, 4/17 long-lasting stable disease following tumour progression 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 cells expanded in the peripheral blood. Furthermore, a diminished pre-treatment ratio of CD4+/CD8+ lymphocytes was normalized during rIL-2 treatment. NK cell activity and lymphokine activated killer (LAK) cell 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 characteristic tumour-induced immunodeficiency. The treatment has proven though limited efficacy in advanced MM. Because most of the responders experienced termination of tumour progression rather than tumour regression, rIL-2 maintenance of chemotherapy-induced remissions should be investigated.
Peest
D
D
Abteilung Immunologie und Transfusionsmedizin, Medizinische Hochschule Hannover, Germany.
Leo
R
R
Bloche
S
S
Hein
R
R
Stannat-Kiessling
S
S
Tschechne
B
B
Fett
W
W
Harms
P
P
Hoffmann
L
L
Bartl
R
R
D000368:Aged; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
D007376:Interleukin-2; D011994:Recombinant Proteins