David O Riley1, Jenna M Schlefman2, Hans Christoph Vitzthum Von Eckstaedt V3, Amy L Morris4, Michael K Keng1, Firas El Chaer5. 1. Department of Medicine, Division of Hematology and Oncology, University of Virginia School of Medicine, 1215 Lee Street, Charlottesville, VA, 22903, USA. 2. Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA. 3. University of Virginia School of Medicine, Charlottesville, VA, USA. 4. Department of Pharmacy Services, UVA Health, Charlottesville, VA, USA. 5. Department of Medicine, Division of Hematology and Oncology, University of Virginia School of Medicine, 1215 Lee Street, Charlottesville, VA, 22903, USA. fe2gh@virginia.edu.
Abstract
PURPOSE OF REVIEW: The incorporation of pegaspargase in chemotherapy regimens has significantly improved the prognosis of ALL in adults. However, pegaspargase use poses many challenges due to its unique toxicity profile. Here, we review pegaspargase's most clinically significant toxicities, and provide guidance for their prevention and management in order to avoid unnecessary drug discontinuation and achieve maximum clinical benefit. RECENT FINDINGS: Clinically significant toxicities of pegaspargase include thrombosis, hypersensitivity and inactivation, hepatotoxicity, pancreatitis, and hypertriglyceridemia. The majority of these toxicities are temporary, nonfatal, and can be managed supportively without permanent pegaspargase discontinuation. Special attention should be paid to inactivation, which can lead to treatment failure, as well as pancreatitis, which necessitates complete cessation of asparaginase therapy. The question of how to best proceed in patients who cannot tolerate pegaspargase remains unanswered, and is an important area of future investigation. Pegaspargase is an essential component of the pediatric-inspired regimens that have improved survival in adult ALL. Although pegaspargase's toxicity profile is unique, it is also highly manageable and should not be a barrier to achieving maximum clinical benefit using this drug.
PURPOSE OF REVIEW: The incorporation of pegaspargase in chemotherapy regimens has significantly improved the prognosis of ALL in adults. However, pegaspargase use poses many challenges due to its unique toxicity profile. Here, we review pegaspargase's most clinically significant toxicities, and provide guidance for their prevention and management in order to avoid unnecessary drug discontinuation and achieve maximum clinical benefit. RECENT FINDINGS: Clinically significant toxicities of pegaspargase include thrombosis, hypersensitivity and inactivation, hepatotoxicity, pancreatitis, and hypertriglyceridemia. The majority of these toxicities are temporary, nonfatal, and can be managed supportively without permanent pegaspargase discontinuation. Special attention should be paid to inactivation, which can lead to treatment failure, as well as pancreatitis, which necessitates complete cessation of asparaginase therapy. The question of how to best proceed in patients who cannot tolerate pegaspargase remains unanswered, and is an important area of future investigation. Pegaspargase is an essential component of the pediatric-inspired regimens that have improved survival in adult ALL. Although pegaspargase's toxicity profile is unique, it is also highly manageable and should not be a barrier to achieving maximum clinical benefit using this drug.
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