Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001.
Lynda M Vrooman, Traci M Blonquist, Kristen E Stevenson, Jeffrey G Supko, Sarah K Hunt, Sarah M Cronholm, Victoria Koch, Samantha Kay-Green, Uma H Athale, Luis A Clavell, Peter D Cole, Marian H Harris, Kara M Kelly, Caroline Laverdiere, Jean-Marie Leclerc, Bruno Michon, Andrew E Place, Marshall A Schorin, Jennifer J G Welch, Donna S Neuberg, Stephen E Sallan, Lewis B Silverman
Author Information
Lynda M Vrooman: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA. ORCID
Traci M Blonquist: Department of Data Science, Dana-Farber Cancer Institute, Boston, MA.
Kristen E Stevenson: Department of Data Science, Dana-Farber Cancer Institute, Boston, MA.
Jeffrey G Supko: Department of Medicine, Massachusetts General Hospital, Boston, MA.
Sarah K Hunt: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Sarah M Cronholm: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Victoria Koch: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Samantha Kay-Green: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Uma H Athale: Division of Pediatric Hematology/Oncology, McMaster University, Hamilton, ON, Canada. ORCID
Luis A Clavell: Division of Pediatric Oncology, San Jorge Children's Hospital, San Juan, Puerto Rico.
Peter D Cole: Division of Pediatric Hematology/Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ. ORCID
Marian H Harris: Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Kara M Kelly: Department of Pediatric Oncology, Roswell Park Cancer Institute and Oishei Children's Hospital, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY. ORCID
Caroline Laverdiere: Division of Hematology and Oncology, Hospital Sainte-Justine, University of Montreal, Montreal, Canada.
Jean-Marie Leclerc: Division of Hematology and Oncology, Hospital Sainte-Justine, University of Montreal, Montreal, Canada.
Bruno Michon: Division of Hematology-Oncology, Centre Hospitalier Universite de Quebec, Quebec City, Canada.
Andrew E Place: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Marshall A Schorin: Inova Fairfax Hospital for Children, Falls Church, VA. ORCID
Jennifer J G Welch: Division of Pediatric Hematology/Oncology, Hasbro Children's Hospital, Brown University Medical School, Providence, RI. ORCID
Donna S Neuberg: Department of Data Science, Dana-Farber Cancer Institute, Boston, MA.
Stephen E Sallan: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Lewis B Silverman: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
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/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% 17%; ˂ .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 ( = .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 ( = .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.
