7368 Triglyceride Tales: Two Cases Unveiling Pegaspargase-Induced Hypertriglyceridemia

Abstract Disclosure: S. Noguchi: None. A. Singh: None. A. Rajpal: None. Introduction: Acute lymphoblastic leukemia (ALL) is a hematologic malignancy that has seen dramatic improvements in survival, owing to the development of multi-agent chemotherapy regimens. Pegaspargase (PEG), an enzyme that depletes serum asparagine and leads to apoptosis of leukemic cells, has long been a cornerstone of ALL chemotherapy regimens. While many toxicities have been recognized including hypersensitivity, thrombosis and hepatotoxicity, hypertriglyceridemia (HTG) is a much less documented complication. We present two patients who developed severe hypertriglyceridemia (sHTG) secondary to PEG, with differing outcomes. Both patients were re-challenged with PEG and again developed sHTG. Case description: A 31-year-old male presented with leukocytosis and blastemia and was diagnosed with Philadelphia chromosome negative B-cell ALL. He underwent chemotherapy induction via pediatric-inspired protocol CALBG 10403 which included PEG. Three weeks later triglyceride (TG) levels rose to 3,728 mg/dl, but normalized with gemfibrozil over the next month. He received two more doses of PEG, separated by four weeks, as part of consolidation chemotherapy. Eleven days following the third dose he presented with abdominal pain, lipase of 702 units/L, TG of 3,999 mg/dl and imaging consistent with necrotizing pancreatitis. With intravenous insulin and meropenem he eventually made a full recovery, however he had a persistent pancreatic pseudocyst. Thereafter, he was transitioned to HyperCVAD followed by POMP maintenance chemotherapy.Another patient, a 35-year-old female presented with cytopenia and was also diagnosed with Philadelphia chromosome negative B-cell ALL. She was also induced with CALBG 10403 protocol including PEG. One month later her TG levels rose to 1,295 mg/dl and was started on fenofibrate. Following resolution of the lipemia, she underwent consolidation chemotherapy which included two doses of PEG administered four weeks apart. Despite a 50% dose reduction, ten days after the third dose TGs rose to a peak of 3,363 mg/dl, however she did not develop pancreatitis. She was treated with intravenous insulin, gemfibrozil and omega-3-acid ethyl esters for sHTG. Given complications with CALGB, she is planned to transition to blinatumomab consolidation. Discussion: Albeit a rare complication of PEG, the presented cases highlight the severity of HTG that can result from this commonly used chemotherapy agent. There are currently no guidelines for the baseline assessment of TG levels in ALL patients receiving PEG. Awareness of this potential complication should prompt regular monitoring of TG levels in patients undergoing regimens involving PEG. There is a need for future studies to identify patients at higher risk of developing sHTG and evaluate the appropriate dose and frequency of PEG administration in patients who develop sHTG after initial exposure. Presentation: 6/3/2024