Safety profile
Adverse reactions (all grades) reported with ONCASPAR® therapy1
MedDRA Standard System Organ Class | Very common (≥1 in 10) |
|---|---|
Blood and lymphatic system disorders | Febrile neutropenia |
Gastrointestinal disorders | Pancreatitis, Diarrhea, Abdominal pain |
Hepatobiliary disorders | |
Immune system disorders | Hypersensitivity, Urticaria, Rash, Anaphylactic reactions |
Infections and infestations | Infections |
Investigations | Alanine aminotransferase increased, Aspartate aminotransferase increased, Blood bilirubin increased, Blood fibrinogen decreased, Lipase increased, International normalized ratio increased, Amylase increased, Activated partial thromboplastin time prolonged |
Metabolism and nutrition disorders | Hyperglycemia, Hypertriglyceridemia, Hypoalbuminemia |
Musculoskeletal and connective tissue disorders | |
Nervous system disorders | |
Respiratory, thoracic and mediastinal disorders | |
Vascular disorders | Embolism¶ |
Adapted from the ONCASPAR® Product Monograph. Please see the ONCASPAR® Product Monograph for full safety information.
¶ The following were observed in clinical trial DFCI 11-001: Pulmonary embolism (common), venous thrombosis (common), venous thrombosis limb (uncommon), thrombophlebitis superficial (uncommon).
|| Including CNS Thrombosis.
Investigations reported as adverse events:1
- Very common: ALT increased, AST increased, blood bilirubin increased, blood fibrinogen decreased, lipase increased, international normalized ratio increased, amylase increased, activated partial thromboplastin time prolonged.
- Common: Neutrophil count decreased, platelet count decreased.
In patients with previously treated ALL and/or hypersensitivity to native E. coli asparaginase1
Adverse reaction information was obtained from clinical trials that enrolled a total of 174 patients with relapsed ALL who received ONCASPAR® as a single agent or in combination with multi-agent chemotherapy. In this group:
- The most common adverse reactions of ONCASPAR® were clinical allergic reactions (bronchospasm, hypotension, laryngeal edema, local erythema or swelling, systemic rash, and urticaria), elevated transaminases, hyperbilirubinaemia, and coagulopathies.
- The most common serious adverse events due to ONCASPAR® treatment were thrombosis (4%), hyperglycaemia requiring insulin therapy (3%), and pancreatitis (1%).
Immunogenicity1
As with all therapeutic proteins, with ONCASPAR® there is a potential for immunogenicity, defined as development of binding and/or neutralizing antibodies to the product.
In Study CCG-1962, ONCASPAR®-treated patients were assessed for evidence of binding antibodies using an enzyme-linked immunosorbent assay (ELISA) method. The incidence of protocol-specified “high-titer” antibody formation was 2% in Induction (n=48), 10% in Delayed Intensification 1 (n=50), and 11% in Delayed Intensification 2 (n=44).
There is insufficient information to determine whether the development of antibodies is associated with an increased risk of clinical allergic reactions, altered pharmacokinetics, or loss of anti-leukemic efficacy.
aBFM: augmented Berlin-Frankfurt-Münster; ALL: acute lymphoblastic leukemia; BSA: body surface area; CNS: central nervous system; CSF: cerebrospinal fluid; DFCI: Dana-Farber Cancer Institute; ELISA: enzyme-linked immunosorbent assay; IM: intramuscular; IV: intravenous; PD: pharmacodynamics; PK: pharmacokinetics; NCCN: National Comprehensive Cancer Network®; TDM: therapeutic drug monitoring.
* Clinical significance has not been established.
† Comparative clinical significance has not been established.
‡ Fictitious cases. May not be representative of all patients.
§ Native E. coli L-asparaginase is not available in Canada.
References:
- ONCASPAR® Product Monograph. Servier Canada. August 20, 2024.
- ONCASPAR_CPID Redacted.
- ASPARLAS® Product Monograph. Servier Canada. March 8, 2024.
- RYLAZE™ Product Monograph. Jazz Pharmaceuticals Canada Inc.
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia V.2.2024. Available at: https://www.nccn.org/professionals/physician_gls/pdf/all.pdf. Accessed November 8, 2024.
- Vrooman LM et al. Efficacy and toxicity of pegaspargase and calaspargase pegol in childhood acute lymphoblastic leukemia: Results of DFCI 11-001. J Clin Oncol. 2021;39(31):3496–3505.
