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Interleukin 12 Immunotherapy after Autologous Stem Cell Transplantation for Hematological Malignancies¹

Bone Marrow and Stem Cell Transplantation Program, Lymphoma Program, and the Division of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202

Purpose: To determine the safety, maximum tolerated dose,and biological effects of recombinant human IL-12 after autologous stem cell transplantation for cancer.

Experimental Design: Twelve patients with hematological malignancies (8 non-Hodgkin’s lymphoma, 2 Hodgkin’s disease, and 2 plasma cell myeloma) began interleukin (IL)-12 therapy at a median of 66 days after transplantation. Recombinant human IL-12 was given by bolus i.v. injection in doses of 30, 100, or 250 ng/kg once as an inpatient and then, after a 2-week hiatus, once daily for 5 consecutive days every 3 weeks on an outpatient basis.

Results: Common side effects included fever, chills, fatigue, nausea or vomiting, and asymptomatic elevation in serum liver function tests. Transient neutropenia and thrombocytopenia were also common, but no patient required platelet transfusion or had a neutropenic fever. Dose-limiting toxicities (diarrhea and elevated liver function tests) occurred in 2 of 3 patients treated in the 250 ng/kg cohort. Biological effects, including increases in serum IFN- levels and transient lymphopenia involving CD4 T cells, CD8 T cells, B cells, and NK cells, were seen at all three dose levels.

Conclusions: Biologically active doses of IL-12 can be given safely to patients after autologous stem cell transplantation for high-risk hematological malignancies. Further studies are indicated to assess the efficacy of IL-12 in this setting.

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