Abstract
Abstract Pegaspargase (peg-asp) is a pegylated form of asparaginase with a longer half-life used in pediatric-inspired chemotherapy for treatment of adult acute lymphocytic leukemia (ALL). Peg-asp appears to confer a survival advantage, but use in older adults is limited by concern for toxicity, though incidence and associated factors are poorly characterized. Our primary objective was to compare peg-asp tolerability in different age groups; secondary objectives were assessment of patient- (pt) and disease-dependent factors associated with toxicity. We retrospectively reviewed 58 ALL pts treated with at least 1 dose of peg-asp (500-2500IU/m2) at our institution between 2016-2021. We used χ-squared- and Fisher’s test, and multivariable regression analysis to assess relationships between pt-factors and toxicities. Median doses received was 2 (range 1-7). 38 pts were 40 years or older, 20 were >60 years. 18 received PEG during induction only, 8 in consolidation only, 27 in both, and 5 during salvage therapy post-relapse. 17 had Philadelphia (Ph) positive B-ALL; 32 Ph negative B-ALL; 7 T-ALL; and 2 had mixed phenotype acute leukemia. Pts were 19-78 years old (median 48.5). Grade 3 or 4 toxicities observed in >10% of cases included hepatotoxicity (81%, 47/58); antithrombin 3 depletion (72.4%, 42/58); hypofibrinogenemia <100 (58.6%, 34/58); hypertriglyceridemia (20.8%, 10/48); venous thromboembolism (12.1%, 7/58) and hemorrhage (12.1%, 7/58). Acute pancreatitis (8.6%, 5/58) and hypersensitivity (2/58, 3.4%) were less common. On univariate analysis, grade 3 liver injury was significantly associated with younger age groups (18-40 and 40-60 vs >60 years; p=0.025), likely due to older age strongly correlating (p <0.01) with receipt of <2000IU/m2 pegaspargase. No other toxicity was significantly associated with age. Hypofibrinogenemia and hepatotoxicity were significantly associated with initial receipt of pegaspargase during induction vs consolidation (p=0.042, p=0.013, respectively) but age was not. Pts receiving a max dose PEG of <2000IU/m2 had significantly lower odds of developing hepatotoxicity and hypertriglyceridemia than those receiving 2000 IU/m2 or more (p=0.008, p=0.003, respectively). On multivariate analysis, higher max dose of PEG received (2000 IU/m2 or over) correlated with greater odds of hepatotoxicity, hypertriglyceridemia and acute pancreatitis (OR 1.72, CI 1.23-2.38; OR 1.31, CI 2.18, CI 1.59-3.03; and OR 1.46, CI 1.13-1.88, respectively). Hypertriglyceridemia was also associated with older age and BMI >30 (OR 1.31, CI 1.05-1.62, and OR 1.31, CI 1.09-1.59, respectively). In summary, low dose pegaspargase is a viable option in ALL in adults over 60, with only hypertriglyceridemia associated with older age. Future work might correlate serum pegaspargase activity to intolerance and outcomes, and examine whether prophylactic treatment e.g. with levocarnitine might prevent toxicity. Citation Format: Yosef Joseph Rene Amel Riazat-Kesh, Hannah Levavi, Sangeetha Venugopal, Carli Beall, Ronald Hoffman, Marina Kremyanskaya, John Mascarenhas, Sara Kim, Michal Bar-Natan. Pegaspargase is a viable option in elderly adults with acute lymphoblastic leukemia. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5517.
