Risk factors for severe neuropsychiatric toxicity in patients receiving interferon alfa-2b and low-dose cytarabine for chronic myelogenous leukemia: Analysis of cancer and leukemia Group B 9013

Purpose: Recombinant interferon alfa-2b (rIFN alpha 2b) is a standard thera py for chronic myelogenous leukemia (CML). Severe neuropsychiatric toxicity has been described in patients receiving rIFN alpha 2b, although the frequ ency of and the risk factors for developing this toxicity are not well desc ribed. The purpose of this study was to identify predictors for the develop ment of severe neuropsychiatric toxicity in CML patients receiving rIFN alp ha 2b-based therapy. Patients and Methods: From a prospective cohort of 91 philadelphia chromoso me-positive, previously untreated, chronic-phase CML patients treated on Ca ncer and Leukemia Group B (CALGB) 9013, a phase II trial of rIFN alpha 2b p lus cytarabine, the following were recorded at baseline: age, sex, race, pr etreatment history of neurologic or psychiatric diagnosis, spleen size, blo od counts, and peripheral blast count. Best response to treatment, rIFN alp ha 2b cumulative dose, dose duration, and dose-intensity were recorded duri ng follow-up. Severe neuropsychiatric toxicity was defined as grade 3 or 4 events, according to CALGB expanded common toxicity criteria. Univariate an d multivariate logistic regression analyses were used to identify variables that were associated with the development of severe neuropsychiatric toxic ity. Results: Severe neuropsychiatric toxicity developed in 22 patients (24.0%; 95% confidence interval [CI], 15.2% to 32.8%), Toxicity resolved after with drawal of treatment in all patients. Five of six patients developed recurre nce of symptoms with rechallenge. Twelve (63%) of 19 patients with a pretre atment neurologic or psychiatric diagnosis developed severe neuropsychiatri c toxicity, as compared with 10(14%) of 72 patients without a pretreatment neurologic or psychiatric diagnosis (P = .001), resulting in a relative ris k of 4.55 (95% CI, 2.33 to 8.88) for developing severe neuropsychiatric tox icity. No other variables were independently associated with the developmen t of neuropsychiatric toxicity. Conclusion: CML patients with a pretreatment history of a neurologic or psy chiatric diagnosis are at significantly increased risk of developing severe neuropsychiatric toxicity during therapy with rIFN alpha 2b plus cytarabin e. Monitoring for neuropsychiatric symptoms and avoiding rechallenge are re commended measures for such patients receiving rIFN alpha 2b-based therapy. (C) 2000 by American Society of Clinical Oncology.