High-Dose IL-2 May Benefit Brain Metastases in Melanoma

John Richart, MD

High doses of interleukin-2 (IL-2) could be used to treat patients with melanoma whose disease has metastasized to the brain, potentially expanding options in a population facing a grim prognosis, according to researchers from Saint Louis University in Missouri.

Investigators retrospectively reviewed outcomes for eight patients with stable melanoma brain metastases who were treated at the university between January 1999 and June 2011 with IL-2 intravenously at 720,000 IU/kg per dose on a regimen of 14 doses and two cycles per course for a maximum of two courses. Of the eight patients, one patient started treatment with lung lesions after resection of melanoma brain disease and had a partial response. The remaining seven patients had brain metastases when they began treatment with the immunotherapy.

The median overall survival (OS) for the cohort was 8.7 months (range, 2.1-19.0 months), and the median OS for those who began treatment with brain metastases was 6.7 months (range, 2.1- 18.2 months). All seven patients in this latter cohort experienced progressive disease. Patients received radiosurgery and whole brain radiation before and after IL-2 therapy.

By contrast, the median OS of patients with melanoma brain metastases is approximately four months with existing treatment options, which typically consist of radiation and surgery, Chu et al reported.

One patient did exhibit symptoms of neurotoxicity, but the investigators later learned of a history of alcohol abuse. When this patient was placed in a withdrawal program, the patient’s symptoms improved. None of the patients who received IL-2 experienced treatment-related mortality, and for most patients, survival after diagnosis of brain metastases and IL-2 initiation was longer than expected when compared with their disease-specific graded prognostic assessment score, researchers said.

“Our study shows that having this condition does not exclude a patient from getting this treatment and can in fact improve the length of their life,” said principal investigator John Richart, MD, associate professor of Internal Medicine at Saint Louis University, in a statement.

Aldesleukin (Proleukin), a genetically engineered form of IL-2, has been approved by the FDA since 1998, with clinical data establishing a 600,000 IU/ kg dosage administered intravenously every eight hours for a maximum of 14 doses. “Currently, it is the only FDAapproved regimen associated with continuous complete remission over long-term follow-up (>5 years),” said Chu et al.

However, only 16% of patients respond to IL-2, and the therapy is associated with toxicities such as capillary leak syndrome, cardiac tachyarrythmias, and seizures, the researchers noted. As a result, it is typically reserved for “a select group of patients with excellent performance status.”

The researchers suggested that further studies in larger cohorts could better determine the role of IL-2 for this patient population, as well as the best use of new therapies that have been approved since the patients in this study were treated. They said prior studies have indicated a cumulative incidence of melanoma brain metastases at <10% of patients overall, but at least one-third to one-half—and possibly as many as 75%&mdash;of patients with advanced melanoma.

Chu MB, Fesler MJ, Armbrecht ES, et al. Highdose interleukin-2 (HD IL-2) therapy should be considered for the treatment of patients with melanoma brain metastases [published online ahead of print May 13, 2013].Chemother Res Pract