IL-2 Shows Promise in Treating Hematologic Cancers

SAN FRANCISCO—The use of interleukin-2 (IL-2, Proleukin) in hematologic malignancies is much less advanced than similar work in metastatic melanoma or renal cell carcinoma.

“There are clear hints that IL-2 may have an effect,” Alexander Fefer, MD, said at the Proleukin First International Congress, sponsored by Chiron Corporation. “Some patients are doing better than we are used to seeing, but this is very soft data, and IL-2 is not an innocuous treatment. I don’t want to overstate the case.”

At the University of Washington and the Fred Hutchinson Cancer Research Center, Seattle, phase I trials of IL-2 following autologous stem cell transplant for non-Hodgkin’s lymphoma (NHL) and acute myelogenous leukemia (AML) have produced what Dr. Fefer called encouraging clinical outcomes.

In NHL, 14 of 24 patients remain in complete remission two to four years after treatment with IL-2. In AML, 10 of 17 patients treated beyond first remission have had no recurrence of disease more than five years after IL-2 treatment.

Results Still Anecdotal

“We were happily surprised, but as impressive as it is, this is still anecdotal.” said Dr. Fefer, professor of medicine, University of Washington School of Medicine. He also noted that the favorable results in AML are inconsistent with those of a more recent trial by the same researchers using a different stem cell source and a different IL-2 formulation. In this study, only four of 16 patients remained in complete remission three years post-treatment.

A multicenter randomized phase III trial of IL-2 versus observation after autologous stem cell transplantation for NHL patients in relapse (SWOG 9438) has recently begun, Dr. Fefer said, and other studies of IL-2 for lymphoma and acute leukemia are planned for the United States and Europe

“Randomized studies are clearly necessary,” Dr. Fefer said. He added that while there is tremendous interest in IL-2 among clinicians, “there is at present no justification for using it in hematologic malignancies except in a formal, clinical research setting.”

Incubating Stem Cells in IL-2

Koen van Besien, MD, associate professor of medicine, University of Illinois, Chicago, has achieved encouraging results in lymphoma patients by incubating bone marrow or stem cells in IL-2 before transplantation, followed by IL-2 therapy immediately after the transplant.

Of 19 non-Hodgkin’s lymphoma patients, eight developed progressive disease, but nine remain free of disease for up to three years after transplant. “We selected for the worst patients,” Dr. van Besien told the congress, noting that 12 of the subjects had refractory lymphoma.

Preclinical work suggested that exposing marrow or stem cells to IL-2 before transplant could purge the graft of drug-resistant tumor cells without affecting its proliferative potential. Continued exposure to IL-2 after engraftment could boost the antitumor effect.

In this study, autologous marrow or stem cells were incubated with 6,000 IU/mL of IL-2 for 24 hours, then transplanted. Immediately after transplantation, patients were given IL-2 (1 to 2 million IU/m²/day) by continuous infusion for at least 21 days, plus G-CSF (Neupo-gen), 5 µg/kg, until neutrophil recovery. After three weeks, patients also received higher maintenance doses of IL-2 for six months. Patients actually received approximately 75% of the prescribed IL-2 dosage because of side effects, primarily fever. Two patients died from treatment-related toxicities.

Dr. Van Besien said that a prospective phase II trial, already underway, may provide information on how to achieve better results with this approach.