Phase II study of autologous transplantation with interleukin-2-incubated peripheral blood stem cells and posttransplantation interleukin-2 in relapsed or refractory non-Hodgkin lymphoma

Abstract

Previous work suggested that interleukin (IL)-2 can be used for eradicating residual disease in autologous grafts and for preventing recurrence. We report a phase II study of autologous peripheral blood stem cell transplantation with in vitro IL-2 incubation of peripheral blood stem cells and posttransplantation IL-2 in patients with recurrent or refractory non-Hodgkin lymphoma. Salvage chemotherapy consisted of ifosfamide and etoposide. Responding patients underwent autologous peripheral blood stem cell transplantation. IL-2-incubated stem cells were infused on day 0. IL-2 1 mIU/m2 was given from day 1 until day 28. Four monthly maintenance cycles of IL-2 4 mIU/m2 subcutaneously twice daily days 1 to 5 and days 8 to 11 were administered thereafter. Eighty-four evaluable patients were enrolled, and 60 proceeded to transplantation, of which 56 received IL-2-incubated stem cells. The average received dose of posttransplantation IL-2 was 30% to 50% of planned. Only 42 patients received maintenance IL-2. The average received maintenance dose of IL-2 was also approximately 30% of planned. Most dose reductions were due to toxicity or patient refusal. Three-year survival and progression-free survival for all registered patients were 43% (95% confidence interval [CI], 33%-53%) and 31% (95% CI, 21%-41%), respectively. For the 60 patients undergoing transplantation, they were 59% (95% CI, 46%-72%) and 44% (95% CI, 31%-57%), respectively. There was no relation between the dose of IL-2 received and outcome. Survival and disease-free survival of the study group were similar to those of a previous study cohort that received unmanipulated stem cells and no systemic IL-2. Administration of IL-2-incubated peripheral blood stem cells and intensive posttransplantation IL-2 was associated with considerable but rapidly reversible toxicity. No effect on long-term outcome was observed.

IL-2 in the therapy of melanoma and other malignancies

“…Initial trials, modeled after the regimens used for solid tumors, showed promise in patients with relapsed acute myelogenous leukemia (AML) [25,26] and lymphomas, including Hodgkin lymphoma [27][28][29][30]. Additional investigations were designed to take advantage of the unique microenvironment provided by these diseases, including the proximity of neoplastic cells to the antigen-presenting cells (APC) and immune effector cells (T and NK) in the blood and marrow [31,32]. Because the early trials in leukemia and lymphoma were encouraging, innovative strategies followed, including the combination of antibody therapy with IL-2 to enhance antibody-dependent cellular cytotoxicity and other potential synergistic interactions.…”

Therapeutic options for patients with hodgkin’s disease and non-hodgkin’s lymphoma who relapse after autologous transplant

“…Despite their clear activity as phase I agents, these drugs have not been shown to have clear benefit in the post-transplant setting. A large phase II study [36] of infusion with IL-2 incubated stem cells followed by post-transplant IL-2 failed to show any benefit. Others are using more innovative approaches for post-transplant immunomodulation.…”

A Randomized Controlled Multicenter Study Comparing Recombinant Interleukin 2 (rIL-2) in Conjunction With Recombinant Interferon Alpha (IFN-α) Versus no Immunotherapy for Patients With Malignant Lymphoma Postautologous Stem Cell Transplantation

“…Although immunostimulatory changes of potential antitumor significance were reported, these researchers did not observe beneficial effects on relapse or survival in comparison with historic controls. 24 A number of other cytokines have shown antitumor activity in lymphoma patients. One of these cytokines, IFN-a, when administered by itself or in conjunction with chemotherapy, has been shown to be effective in evoking antitumor response in 40% to 50% of the patients with low-grade NHL studied, including CR in 5% to 10% of these patients.…”