Introduction
Calaspargase pegol-mknl is a long-acting asparagine-specific enzyme indicated as a component of multi-agent chemotherapeutic regimens for the treatment of acute lymphoblastic leukemia (ALL). It is a modified version of L-asparaginase conjugated with monomethoxypolyethylene glycol (PEG), designed to provide prolonged asparagine depletion with potentially reduced immunogenicity compared to native forms.
Mechanism of Action
Calaspargase exerts its antineoplastic effect through enzymatic hydrolysis of L-asparagine into aspartic acid and ammonia. Leukemic cells, particularly lymphoblasts, have reduced ability to synthesize asparagine due to low expression of asparagine synthetase and are therefore dependent on exogenous sources of this amino acid. Depletion of circulating asparagine results in inhibition of protein synthesis, ultimately leading to cytotoxic effects and cell death in susceptible leukemic cells.
Indications
Calaspargase is FDA-approved for use as a component of multi-agent chemotherapeutic regimens for the treatment of:
- Newly diagnosed acute lymphoblastic leukemia (ALL) in pediatric and young adult patients aged 1 month to 21 years
Dosage and Administration
Standard dosing: 2,500 U/m² intravenously over 1 hour every 21 days Administration:- For intravenous infusion only
- Administer over 1 hour through a dedicated line
- Do not administer as an intravenous push or bolus
- Do not mix with other medications
- Use 0.9% Sodium Chloride Injection, USP as diluent
- Hepatic impairment: Use with caution and monitor closely
- Renal impairment: No specific dosage adjustment recommended
- Geriatric patients: Limited data available
- Obese patients: Use actual body surface area for dosing
Pharmacokinetics
Absorption: Administered intravenously, resulting in complete bioavailability Distribution: Volume of distribution approximately 2.0-2.5 L; limited extravascular distribution due to large molecular size Metabolism: Metabolized via proteolytic degradation; PEG component is not metabolized Elimination: Terminal half-life approximately 16 days; primarily cleared through the reticuloendothelial system Special considerations: Prolonged asparaginase activity duration compared to native forms (approximately 2-3 weeks)Contraindications
- History of serious hypersensitivity reactions to calaspargase pegol-mknl
- History of serious pancreatitis with previous L-asparaginase therapy
- History of serious thrombosis with previous L-asparaginase therapy
- History of serious hemorrhage with previous L-asparaginase therapy
- Severe hepatic impairment
Warnings and Precautions
Hypersensitivity reactions: Serious reactions including anaphylaxis can occur; monitor closely during and after infusion Pancreatitis: Fatal cases reported; monitor for abdominal pain, nausea, and vomiting Thrombosis: Serious thrombotic events including sagittal sinus thrombosis can occur Hemorrhage: Increased risk of bleeding events; monitor coagulation parameters Hepatotoxicity: Elevations in transaminases and bilirubin common; may require dose modification Hyperglycemia: May require insulin therapy; monitor blood glucose Immunosuppression: Increased risk of infectionsDrug Interactions
Corticosteroids: May increase hyperglycemia risk Anticoagulants: Increased bleeding risk; avoid concurrent use Aspirin/NSAIDs: Increased bleeding risk; use with caution Hepatotoxic drugs: Potential additive hepatotoxicity Vaccines: Avoid live vaccines during therapy Methotrexate: May decrease efficacy if administered concurrently; sequence appropriatelyAdverse Effects
Common (≥20%):- Elevated transaminases
- Hyperbilirubinemia
- Hypoalbuminemia
- Pancreatitis
- Hyperglycemia
- Coagulopathy
- Fever
- Nausea/vomiting
- Hypersensitivity reactions
- Anaphylaxis
- Severe pancreatitis
- Thrombosis (including cerebral sinus thrombosis)
- Severe hemorrhage
- Hepatic failure
- Diabetic ketoacidosis
Monitoring Parameters
Prior to each dose:- Complete blood count with differential
- Liver function tests (AST, ALT, bilirubin, albumin)
- Amylase and lipase
- Fibrinogen and coagulation parameters
- Blood glucose
- Physical examination
- Vital signs every 15 minutes
- Monitor for hypersensitivity reactions
- Continue monitoring for delayed reactions
- Nutritional assessment
- Neurological assessment for thrombotic events
Patient Education
- Report immediately any signs of allergic reaction (rash, itching, swelling, difficulty breathing)
- Monitor for abdominal pain, nausea, or vomiting (possible pancreatitis)
- Report unusual bleeding or bruising
- Be aware of increased infection risk; avoid sick contacts
- Monitor for signs of hyperglycemia (increased thirst, urination)
- Maintain adequate hydration
- Report severe headaches or neurological symptoms
- Inform all healthcare providers about calaspargase therapy
- Do not receive live vaccines during treatment
- Use reliable contraception during and after treatment
References
1. FDA prescribing information: Calaspargase pegol-mknl (2018) 2. Angiolillo AL, et al. J Clin Oncol. 2014;32(34):3874-3882 3. Vrooman LM, et al. Blood. 2018;132(Supplement 1):267 4. Silverman LB, et al. J Clin Oncol. 2010;28(20):3256-3263 5. NCCN Clinical Practice Guidelines in Oncology: Acute Lymphoblastic Leukemia (2023) 6. Asselin BL, et al. Leuk Lymphoma. 2011;52(12):2237-2253 7. Liu Y, et al. Clin Pharmacokinet. 2012;51(12):809-816
This information is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for personalized medical guidance.