Pilot Study to Evaluate rIL-2 Maintenance Therapy Following Chemotherapy with Vincristine, Adriamycin, and Decadron (VAD) for Multiple Myeloma ( Closed to Accrual and awaiting data maturation)
There is no curative therapy available for multiple myeloma. Maintenance with chemotherapy after initial response is not effective in controlling the disease and carries significant risks.
The myeloma cell is controlled by several immune cells and proteins. There is data to suggest that patients have a disrupted immune system. Also, information is accumulating quickly to suggest a role for cytokines (proteins controlling the immune system) in maintaining multiple myeloma in an inactive state following the initial decrease of tumor load by chemotherapy.
The purpose of the study is to evaluate the role of IL-2 in controlling the disease and keeping it in a stable phase by reorganizing the immune system.
Induction Phase (Chemotherapy with VAD)
Maintenance Phase (Therapy with IL-2)
Induction Phase (Chemotherapy with VAD)
Maintenance Phase ( Therapy with IL-2)
The patient will be evaluated within three weeks prior to entry. Any one of the following conditions eliminates a patient from participating in this protocol.
Allowable Concomitant Therapy
Natural Interleukin-2 is a lymphokine which is produced and secreted by T lymphocytes1. This glycoprotein molecule is intimately involved in the induction of virtually all immune responses in which T cells play a role. Recombinant human Interleukin-2 (rIL-2) has been tested in murine model systems both as primary anti-tumor therapy and as an adjunct to various other therapeutic modalities including chemotherapy and adoptive Immunotherapy with cultured cytotoxic cells. Each of these types of studies indicate that in certain circumstances, rIL-2 has anti-tumor effectiveness.
Recombinant Interleukin-2 has been found in some murine tumor models to be effective as an anti-tumor agent when administered by itself. This has been demonstrated in both pulmonary and hepatic metastatic tumor models and in several other primary murine tumors(2,3). Tumor regression may be mediated by lymphokine-activated killer cells (CD56+) which are induced by IL-2 treatment.
IL-2 has been used recently in the treatment of various hematologic malignancies. Of particular interest is its use as remission maintenance therapy for leukemia and lymphomas (4,5).
Use Of IL-2 in Multiple Myeloma: "Rationale"
Available data suggest that high serum IL-2 levels is one of the most useful predictor indices for longer survival in multiple myeloma patients. In particular, 87% of the multiple myeloma patients with IL-2 serum levels > 10 U/ML were alive at 5 years, while only 13% of the remaining patients with IL-2 < 10 U/ML were alive. This data may reflect the existence of an active T-cell response to B-cell neoplasia, and suggest that the use of IL-2 as a therapeutic strategy for multiple myeloma might have a significant impact on the disease (6). This has led to the consideration of use of IL-2 in the therapy of Multiple Myeloma. Few patients have received IL-2 for induction or consolidation.
IL-2 As Maintenance Therapy in Multiple Myeloma:
There is only preliminary data on the effects of IL-2 in multiple myeloma. Gottlieb, et al have administered IL-2 to 4 patients with multiple myeloma after autologous bone marrow transplantation. The 4 patients received seven infusions of IL-2 after autologous bone marrow transplant. IL-2 infusions were initiated 29-119 days past autologous bone marrow transplantation at doses varying from 1.0 to 2.0 x 106 U/day by continuous infusion for 3-5 days. Increases in natural killer cells and lymphokine activated killer activity of peripheral blood mononuclear cells occurred during IL-2 infusion. IL-2 infusion also induced substantial increase in the production of the cytokine TNF, and g-interferon from peripheral blood lymphocytes. They have demonstrated that malignant plasma cells isolated from patients with multiple myeloma are sensitive to lysis by IL-2 induced LAK cells, derived from patients peripheral blood mononuclear cells. In addition, the thymidine uptake and survival of myeloma cells was reduced by tumor necrosis factor and gamma interferon, two cytokines produced by lymphocytes following exposure to IL-2. They have not shown any evidence that IL-2 induces the growth of clones of malignant plasma cells (7).