Efforts to improve the rate of remission and reduce the risk of relapse in patients with advanced hematologic malignancies are focusing on interleukin-2 (IL-2, aldesleukin, Proleukin), said Alexander Fefer, MD, of the University of Washington Medical School and Fred Hutchinson Cancer Research Center, Seattle.
Efforts to improve the rate of remission and reduce the risk ofrelapse in patients with advanced hematologic malignancies arefocusing on interleukin-2 (IL-2, aldesleukin, Proleukin), saidAlexander Fefer, MD, of the University of Washington Medical Schooland Fred Hutchinson Cancer Research Center, Seattle.
Administered after autologous bone marrow or peripheral bloodstem cell transplantation (which Dr. Fefer collectively refersto as autologous stem cell transplantation or ASCT), IL-2 mayinduce a therapeutic graft-versus-tumor reaction and prevent relapses,he said at the Chemotherapy Foundation's 13th annual symposium.
Although ASCT is widely used in acute myelogenous leukemia (AML)and non-Hodgkin's lymphoma (NHL), these treatments are limitedby their high and early relapse rate. Such relapses may be dueto residual host tumor cells that survived chemotherapy and radiotherapyor the progeny of clonogenic tumor cells transferred with contaminatedmarrow or stem cells, Dr. Fefer said.
In phase I/II trials, IL-2 induced a variety of immunomodulatoryeffects. It appears to stimulate lymphokine-activated killer (LAK)cells and induce secretion of secondary cytokines. It has beenshown to be effective against minimal residual disease, whichis common after ASCT, and it is hoped that it will also be effectiveagainst clonogenic tumor cells, he said. Toxicity in these trialswas significant, though reversible.
Phase III Trials
An intergroup phase III trial has been initiated by the SouthwestOncology Group (SWOG) and the Eastern Cooperative Oncology Group(ECOG) in post-ASCT patients with AML and high risk for relapse.
Patients will be conditioned with busulfan (Myleran) and cyclophosphamide,and will receive bone marrow or peripheral blood stem cells. Oncethey have exhibited engraftment and recovered from toxicity, theywill be randomized to receive one course of IL-2 or to be observed.
Because high-dose IL-2 has induced toxicity serious enough torequire hospitalization, a high induction dose (9 million IU/m²/dayas a continuous IV infusion) will be administered on an inpatientbasis on days 1 to 4. A lower maintenance dose (1.6 × 106IU/m²/day as a continuous IV infusion) will be given on days9 to 18 on an outpatient basis.
A second phase III trial initiated by SWOG is studying post-transplantIL-2 in NHL, Dr. Fefer said. Patients with low, intermediate-,or high-grade NHL at high risk for post-transplant relapse willbe conditioned with total body irradiation, etoposide (VePesid),and cyclophosphamide, and then receive peripheral blood stem cells.
After engraftment and recovery from toxicity, they will be randomizedto IL-2 therapy or observation. The IL-2 regimen will be givenaccording to the same schedule as in the AML trial.
Dr. Fefer said that although this investigational approach isin its earliest stages, "the results of the trials may haveimportant implications for ASCT and, possibly, for the treatmentof hematologic malignancies in clinical settings other than ASCT."