Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001

PURPOSE Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia (ALL) Consortium Protocol 11-001 assessed efficacy and toxicity of calaspargase pegol (calaspargase), a novel pegylated asparaginase formulation with longer half-life, compared with the standard formulation pegaspargase. METHODS Patients age 1 to <= 21 years with newly diagnosed ALL or lymphoblastic lymphoma were randomly assigned to intravenous pegaspargase or calaspargase, 2,500 IU/m(2)/dose. Patients received one induction dose. Beginning week 7, pegaspargase was administered every 2 week for 15 doses and calaspargase every 3 week for 10 doses (30 weeks). Serum asparaginase activity (SAA) (>= 0.1 IU/mL considered therapeutic) was assessed 4, 11, 18, and 25 days after the induction dose and before each postinduction dose. RESULTS Between 2012 and 2015, 239 eligible patients enrolled (230 ALL, nine lymphoblastic lymphoma); 120 were assigned to pegaspargase and 119 to calaspargase. After the induction dose, SAA was >= 0.1 IU/mL in a 95% of patients on both arms 18 days after dosing. At day 25, more patients had SAA >= 0.1 IU/mL with calaspargase (88% v 17%; P .001). Postinduction, median nadir SAAs were similar (>= 1.0 IU/mL) for both arms. Of 230 evaluable patients, 99% of pegaspargase and 95% of calaspargase patients achieved complete remission (P = .12), with no difference in frequency of high end-induction minimal residual disease among evaluable patients with B acute lymphoblastic leukemia (B-ALL). There were no differences in frequencies of asparaginase allergy, pancreatitis, thrombosis, or hyperbilirubinemia. With 5.3 years median follow-up, 5-year event-free survival for pegaspargase was 84.9% (SE +/- 3.4%) and 88.1% (+/- SE 3.0%) for calaspargase (P = .65). CONCLUSION Every 3-week calaspargase had similar nadir SAA, toxicity, and survival outcomes compared with every 2-week pegaspargase. The high nadir SAA observed for both preparations suggest dosing strategies can be further optimized. (C) 2021 by American Society of Clinical Oncology