Low-dose recombinant interleukin-2 therapy in advanced multiple myeloma

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Autologous T-lymphocytes exhibit anti-tumour activity in multiple myeloma (MM).
• Standard chemotherapy often fails in advanced MM, necessitating novel therapeutic strategies.

Purpose of the Study:

• To evaluate the feasibility and immunological effects of low-dose recombinant interleukin-2 (rIL-2) in MM patients.
• To assess tumour response induction by rIL-2 in advanced MM.
• To investigate rIL-2's impact on immune parameters in the context of MM-induced immunodeficiency.

Main Methods:

• A phase I/II trial involving 18 advanced MM patients who failed standard chemotherapy.
• Subcutaneous administration of low-dose rIL-2 (9 x 10(6) IU/m2 twice daily days 1-2, then 0.9 x 10(6) IU/m2 twice daily days 3-56, repeated every 12 weeks).
• Monitoring of immunological parameters, including cell counts, activation markers, NK cell activity, LAK cell activity, and IL-2 production.

Main Results:

• 6/17 patients showed tumour response (2 objective reduction, 4 stable disease).
• Significant increases in eosinophils, activated CD4+ T lymphocytes (CD25 expression), and expanded CD56+ NK cells.
• Normalization of CD4+/CD8+ T-lymphocyte ratio, enhanced NK and LAK cell activity, and induced endogenous IL-2 production.
• Treatment was feasible with no serious side-effects over a mean of 241 days.

Conclusions:

• Low-dose rIL-2 can stimulate immune enhancement in MM, overcoming tumour-induced immunodeficiency.
• The treatment demonstrated limited efficacy in advanced MM, primarily stabilizing disease progression.
• Further research into rIL-2 for maintaining chemotherapy-induced remissions is warranted.