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Less-frequent dosing of a novel pegylated asparaginase is as safe and effective as standard pegylated asparaginase for the treatment of younger, newly diagnosed patients with acute lymphoblastic leukemia (ALL), according to researchers who presented their results at the 2019 American Association of Clinical Oncology Annual Meeting in Chicago, Illinois.1
Because ALL and lymphoblastic lymphoma cells depend on exogenous sources of the amino acid L-asparagine for survival, use of asparaginase, a hydrolase that converts asparagine to aspartic acid in the peripheral blood and cerebrospinal fluid (CSF), has been shown to be an effective approach in combination with multiagent chemotherapy for the treatment of patients with these diseases. Furthermore, a derivative of asparaginase linked to polyethylene glycol (ie, standard pegaspargase) was previously approved by the US Food and Drug Administration (FDA) for children with ALL based on results of a randomized clinical study comparing it with native asparaginase isolated from Escherichia coli.2
In the DFCI 11-001 randomized phase 2 study (ClinicalTrials.gov Identifier: NCT01574274), the efficacy and safety of intravenous (IV) administration of calaspargase pegol, a novel pegylated form of asparaginase with a prolonged half-life (SC-PEG), was compared with IV standard pegaspargase (SS-PEG), in children and adolescents (aged 1 to 21 years) with lymphoblastic leukemia and lymphoblastic lymphoma.
While patients assigned to either arm received 1 induction dose of drug in the first month of treatment, SC-PEG and SS-PEG were subsequently administered every 3 weeks and 2 weeks, respectively, starting at week 7, for a total of 30 weeks of treatment.
Following the induction dose, assessments of serum asparaginase activity were made on days 4, 11, 18, and 25, and prior to each subsequent dose of asparaginase in the postinduction period.
In addition, minimal residual disease was assessed in all patients with B-ALL at the end of induction. The primary outcome measures of the study were asparaginase-related toxicity and asparaginase pharmacokinetics.
Of the 239 patients enrolled in the study, 230 had a diagnosis of ALL; patients were assigned in a 1:1 ratio to each treatment arm.
While serum asparaginase activity remained at the level believed to be necessary for adequate asparagine depletion in plasma and CSF (≥0.1 IU/mL) through day 18 in at least 95% of patients receiving either treatment, significantly fewer patients receiving SS-PEG had therapeutic serum asparaginase activity (17%) at day 25 following the first dose compared with those receiving SC-PEG (88%; P <.001).
In the postinduction period, nadir serum asparaginase activity was similar in patients receiving either form of asparaginase (>1.0 IU/mL), and considerably higher than necessary, suggesting a need for further dose modifications. Regarding minimal residual disease at the end of induction in patients with B-ALL, when the 2 drugs were compared, there were no significant differences observed between them (10.3% [SS-PEG]; 9.5% [SC-PEG]; P =1.0).
At a median follow-up of 4 years, there were no significant differences between the rates of 4-year event-free survival (90.2% [SS-PEG] vs 87.7% [SC-PEG]; P =.78), or overall survival (95.6% [SS-PEG] vs 94.8% [SC-PEG]; P =.74) for the 2 pegylated asparaginase preparations. In addition, complete remission rates were similar across the 2 groups (ie, 99% [SS-PEG] vs 95% [SC-PEG]; P =.12)
With respect to safety, there were no differences in the rates of asparaginase allergy, pancreatitis, thrombosis, hyperbilirubinemia, osteonecrosis, or infection observed in patients across both study arms.
Based in part on these results, in December 2018, the FDA approved SC-PEG for use in children and young adults with ALL.3
- Vrooman LM, Blonquist TM, Supko JG, et al. Efficacy and toxicity of pegaspargase and calaspargase pegol in childhood acute lymphoblastic leukemia/lymphoma: Results of DFCI 11-001. Presented at: 2019 American Society of Clinical Oncology Annual Meeting. May 31-June 3, 2019; Chicago, IL. Abstract 10006.
- Dinndorf PA, Gootenberg J, Cohen MH, et al. FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist. 2007;12:991-998.
- Calaspargase pegol [package insert]. Boston, MA; Servier Pharmaceuticals, LLC. 2018
This article originally appeared on Cancer Therapy Advisor