Neuropsychiatric side effects of high-dose IL-2 on patient with advanced melanoma or renal cell carcinoma.

Abstract

e19030 Background: Treatment of patients with end stage renal cell carcinoma (RCC) or melanoma remains difficult. Immunotherapy with high-dose bolus interleukin (IL-2) is the first biological product clinically approved for the treatment of these cancers. Although effective in 15-20% of patients, high-dose IL-2 treatment has significant neuropsychiatric side effects that mandate treatment cessation. Currently, there is little information available on patients who are prone to these neuro-psychiatric side effects. The main objective was to investigate whether occult brain metastases predispose the patient to developing neuro-psychiatric side effects. Methods: We performed retrospective medical chart reviews of patients who had either RCC or malignant melanoma. Variables considered include patient demographics, cancer type, IL-2 treatment, response to treatment, location of metastasis, prior surgery, prior psychiatric history, and substance abuse. We conducted multivariable log-binomial regression analyses to examine the association between risk factors and neuro-psychiatric side effects. Results: Our study population included 261 cancer patients, among them 54% had melanoma (N=141) and 31% had post neuro-psychiatric disorders (N=81). We found that nicotine abstinence in past smokers (remission) was significantly associated with increased neuro psychiatric side-effects (RR=1.88, P=.015) among melanoma patients, but not RCC patients. The multivariable regression analysis showed that having pre-existing psychiatric disorders was the only factor significantly associated with neuropsychiatric effects (aRR=1.92, P<0.0001), after adjusting for potential confounders. Having brain metastasis, however, was not significantly associated with neuropsychiatric effects (aRR=1.10, P=0.627). Conclusions: Contrary to our original hypothesis, prior psychiatric history was the only significant factor predisposing patients to develop neuro-psychiatric side effects during IL-2 treatment and not occult brain metastases. Future studies with larger patient numbers and longitudinal design will help to refine the findings from this research.