Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia

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Abstract

Purpose: Asparaginase treatment is standard in all pediatric acute lymphoblastic leukemia (ALL) regimens, whereas in adults, it is either excluded or administered for a shorter duration. Several adult ALL protocols are adapting pediatric regimens, but the optimal implementation of asparaginase is not well studied, considering its potential higher toxicity. We studied a pegaspargase dosing strategy based on its pharmacokinetic characteristics in adults. Patients and Methods: Between 2004 and 2009, 51 adults age 18 to 57 years with newly diagnosed ALL were treated with a regimen adapted from a pediatric trial that included six doses of intravenous pegaspargase at 2,000 IU/m2 per dose. Intervals between doses were longer than 4 weeks and rationally synchronized with other chemotherapy drugs to prevent overlapping toxicities. Pegaspargase was administered with steroids to reduce hypersensitivity. Asparaginase-related toxicities were monitored after 173 pegaspargase doses. Results: The most common grade 3/4 asparaginase-related toxicities were lengthy hyperbilirubinemia and transaminitis, occasionally resulting in subsequent treatment delays. All toxicities resolved spontaneously. Forty-five percent of patients were able to receive all six doses of pegaspargase, and 61% received ≥ three doses. In only 20% of patients, the drug was discontinued after pegaspargase-related serious toxicity. Ninety-six percent achieved complete remission, almost all within 4 weeks, and a low induction death rate was seen. Seven-year disease-free and overall survival were 58% and 51%, respectively. Conclusion: Our dose and schedule of pegaspargase, based on its pharmacokinetics, and our detailed toxicity profile could be applied for safer adaptation of pediatric ALL protocols in adults. © 2014 by American Society of Clinical Oncology.

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Douer, D., Aldoss, I., Lunning, M. A., Burke, P. W., Ramezani, L., Mark, L., … Mohrbacher, A. M. (2014). Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia. Journal of Clinical Oncology, 32(9), 905–911. https://doi.org/10.1200/JCO.2013.50.2708

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