Safety and Efficacy of High-Dose Interleukin-2 Therapy in Patients With Brain Metastases

Abstract

The authors determined the safety and efficacy of recombinant high-dose interleukin-2 administration in patients with brain metastases. This retrospective review included 1,069 patients with metastatic melanoma or renal cell carcinoma who received high-dose interleukin-2 alone or in combination with other immunotherapy or chemotherapy from July 1985-July 2000. All patients were evaluated for both toxicity and response. Only the first exposure to interleukin-2 was considered. Parameters evaluated among the groups included toxicity profiles, reasons for stopping treatment, number of interleukin-2 doses per cycle, and response to therapy. Three patient groups were compared. Group 1 (n = 27) comprised patients with previously treated brain metastases (surgery or radiation), group 2 (n = 37) comprised patients with untreated brain metastases, and group 3 (n = 1,005) comprised patients without brain metastases. For most comparisons between patients with brain metastases and those without, no significant differences were noted in toxicity profiles or reasons for stopping interleukin-2 therapy. Patients with previously treated brain metastases received fewer interleukin-2 doses per cycle (median, 6.5) than patients with previously untreated brain metastases (median, 7.5) or patients without brain metastases (median, 7.5). Patients with previously treated brain metastases demonstrated an 18.5% overall clinical response to interleukin-2 treatment. However, patients with evaluable (previously untreated) brain metastases had an overall 5.6% response rate, which was less than the 19.8% response rate of patients without brain metastases. Two of thirty-six patients with evaluable brain metastases demonstrated objective regression of intracranial and extracranial disease after receiving interleukin-2. Carefully selected patients with brain metastases can safely receive high-dose interleukin-2, and some can experience a response to treatment at intracranial and extracranial disease sites. Keywords Interleukin; 2; Melanoma; Brain metastases; Safety Metastatic central nervous system lesions are a common complication of malignant disease and represent a significant cause of morbidity and mortality. Brain metastases are detected clinically in 8%-46% of patients with malignant melanoma (1). Brain metastases develop in 8% of patients with cutaneous melanoma as the first site of distant disease, with a subsequent median survival of 5 months that decreases to 1.4 months if extracranial metastatic disease is present (2). The incidence of brain metastases in patients with renal cell carcinoma is 10%-13% (3). Patients with brain metastases have generally been excluded from treatment with

High dose interleukin-2 (Aldesleukin) - expert consensus on best management practices-2014

“…Patients with brain metastases were often considered not to be candidates, however, with the advent of stereotactic radiotherapy, an asymptomatic patient with adequately treated isolated brain metastases and off systemic corticosteroids can be considered for treatment. Similarly, patients with small untreated brain metastases that are limited in number and causing minimal or no edema may be considered for IL-2 treatment [40].…”

Immune Checkpoint Blockade in Patients With Melanoma Metastatic to the Brain

“…Due to historical concerns about the prognosis of patients with MBM as well as uncertainty about the mechanisms of activity of IL-2, its toxicities (particularly fluid retention and capillary leak syndrome that could exacerbate peritumoral edema) and the potential that the brain is a sanctuary site protected by the BBB, there has been little experience with the use of high-dose IL-2 (HDIL-2) in patients with MBM. A single small series reported a lower than expected rate of activity for HDIL-2 among patients with active MBM but without undue CNS toxicity; the activity and toxicities of HDIL-2 in a small number of patients with MBM controlled prior to IL-2 therapy by surgery/SRS appeared as expected for patients without brain metastases (16). Although HDIL-2 is still used in selected centers as part of an adoptive T cell therapy strategy, these regimens have traditionally excluded patients with MBM for many reasons similar to those detailed for HDIL-2 alone.In many centers, the use of HDIL-2 has been essentially supplanted by the advent of immune checkpoint blocking agents such as antibodies blocking CTLA4 and the newer investigational antibodies that block the PD-1/PD-L1 axis, so the role of HDIL-2 for melanoma patients in general and for those with brain metastases in particular has been called into question.…”

Asymptomatic brain metastases in patients with cutaneous metastatic malignant melanoma

“…MRI-detected CT-negative brain metastases represent a group of patients with low-volume disease. This group can be treated safely with IL-2-based therapy [19]. The routine use of 18 F-fluorodeoxyglucose positron emission tomography for staging of melanoma is increasing, although the resolution for brain metastases makes this modality insufficient for use as an imaging procedure for the detection of brain metastases.…”