Lynda M Vrooman1,2, Traci M Blonquist3, Kristen E Stevenson3, Jeffrey G Supko4, Sarah K Hunt1, Sarah M Cronholm1, Victoria Koch1, Samantha Kay-Green1, Uma H Athale5, Luis A Clavell6, Peter D Cole7, Marian H Harris8, Kara M Kelly9, Caroline Laverdiere10, Jean-Marie Leclerc10, Bruno Michon11, Andrew E Place1,2, Marshall A Schorin12, Jennifer J G Welch13, Donna S Neuberg3, Stephen E Sallan1,2, Lewis B Silverman1,2. 1. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA. 2. Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School Boston, MA. 3. Department of Data Science, Dana-Farber Cancer Institute, Boston, MA. 4. Department of Medicine, Massachusetts General Hospital, Boston, MA. 5. Division of Pediatric Hematology/Oncology, McMaster University, Hamilton, ON, Canada. 6. Division of Pediatric Oncology, San Jorge Children's Hospital, San Juan, Puerto Rico. 7. Division of Pediatric Hematology/Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ. 8. Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA. 9. Department of Pediatric Oncology, Roswell Park Cancer Institute and Oishei Children's Hospital, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY. 10. Division of Hematology and Oncology, Hospital Sainte-Justine, University of Montreal, Montreal, Canada. 11. Division of Hematology-Oncology, Centre Hospitalier Universite de Quebec, Quebec City, Canada. 12. Inova Fairfax Hospital for Children, Falls Church, VA. 13. Division of Pediatric Hematology/Oncology, Hasbro Children's Hospital, Brown University Medical School, Providence, RI.
Abstract
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/m2/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 ≥ 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.
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/m2/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 ≥ 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.
Authors: Netanya I Pollock; Yael Flamand; Jia Zhu; Kate Millington; Kristen Stevenson; Lewis B Silverman; Lynda M Vrooman; Laurie E Cohen Journal: Pediatr Blood Cancer Date: 2021-12-21 Impact factor: 3.838
Authors: Hope D Swanson; Hana Hakim; Diego R Hijano; Ted Morton; Shane Cross; Hiroto Inaba; Sima Jeha; Ching-Hon Pui; Seth E Karol Journal: Cancer Med Date: 2022-07-15 Impact factor: 4.711
Authors: Melissa A Burns; Andrew E Place; Kristen E Stevenson; Alejandro Gutiérrez; Suzanne Forrest; Yana Pikman; Lynda M Vrooman; Marian H Harris; Sarah K Hunt; Jane E O'Brien; Barbara L Asselin; Uma H Athale; Luis A Clavell; Peter D Cole; Lisa M Gennarini; Justine M Kahn; Kara M Kelly; Caroline Laverdiere; Jean-Marie Leclerc; Bruno Michon; Marshall A Schorin; Maria Luisa Sulis; Jennifer J G Welch; Donna S Neuberg; Stephen E Sallan; Lewis B Silverman Journal: Pediatr Blood Cancer Date: 2020-10-07 Impact factor: 3.167