U.S. Food and Drug Administration (FDA)-Approved Indications
Asparlas is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) in pediatric and young adult patients age 1 month to 21 years. Compendial Uses
Lymphoblastic lymphoma (managed in the same manner as ALL) Acute lymphoblastic leukemia (ALL) as a substitute for pegaspargase in patients 21 years and younger for more sustained asparaginase activity Pediatric acute lymphoblastic leukemia (ALL) as a substitute for pegaspargase in patients age 1 month to 21 years for more sustained asparaginase activity Calaspargase pegol-mknl is available as Asparlas (Servier Pharmaceuticals LLC) and is an asparagine specific enzyme indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia in pediatric and young adult patients age 1 month to 21 years. Calaspargase pegol contains an asparagine specific enzyme derived from Escherichia coli, as a conjugate of L-asparaginase (L-asparagine amidohydrolase) and monomethoxypolyethylene glycol (mPEG) with a succinimidyl carbonate (SC) linker. L-asparaginase is an enzyme that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia. The pharmacological effect of Asparlas is thought to be based on selective killing of leukemic cells due to depletion of plasma L-asparagine. Leukemic cells with low expression of asparagine synthetase have a reduced ability to synthesize L-asparagine, and therefore depend on an exogenous source of L-asparagine for survival (Servier Pharmaceuticals, 2020).
Per the prescriber information, calaspargase pegol-mknl (Asparlas) carries the following contraindications:
History of serious hypersensitivity reactions to pegylated L-asparaginase History of serious thrombosis during L-asparaginase therapy History of serious pancreatitis related to previous L-asparaginase treatment History of serious hemorrhagic events during previous L-asparaginase therapy Severe hepatic impairment Per the prescring information, warnings and precautions include:
Hypersensitivity: Grade 3 and 4 hypersensitvity reactions including anaphylaxis have been noted in clinical trials with Asparlas with an occurrence between 7% to 21%. Pancreatitis: Cases of pancreatitis have been noted in clinical trials with Asparlas with an occurrence between 12 to 16%. Thrombosis: Serious thrombotic events, including sagittal sinus thrombosis, have been noted in clinical trials with Asparlas wih an occurrence of 9 to 12%. Hemorrhage Hepatotoxicity Per the prescribing information, the most common (occurrence ≥ 10%) grade ≥ 3 adverse reactions were elevated transaminase, bilirubin increased, pancreatitis and abnormal clotting studies.
The determination of efficacy was based on a demonstration of the achievement and maintenance of nadir serum asparaginase activity (NSAA) above the level of 0.1 U/mL using Asparlas 2500 U/m
2 intravenously every 3 weeks. The pharmacokinetics of Asparlas were studied when used in combination with multiagent chemotherapy in 124 patients with B cell lineage acute lymphoblastic leukemia (ALL). Among these patients, the median age was 11.5 years (range 1 – 26); 62 (50%) were male, 102 (82%) white, 6 (5%) Asian, 5 (4%) Black or African American, 2 (2%) Native Hawaiian or Pacific Islander and 9 (7%) other or unknown. The results showed that 123 (99%, 95% CI: 96% - 100%) of the 124 patients maintained NSAA > 0.1 U/mL at weeks 6, 12, 18, 24 and 30.
Criteria for Initial Approval
Aetna considers calaspargase pegol - mknl (Asparlas) medically necessary for the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma when all of the following criteria are met: The requested medication will be used in conjunction with multi-agent chemotherapy; and The member is 21 years of age or younger. Aetna considers all other indications as experimental and investigational.
Continuation of Therapy
Aetna considers continued calaspargase pegol - mknl (Asparlas) therapy medically necessary for an indication listed in Section I when there is no evidence of unacceptable toxicity or disease progression while on the current regimen. Dosage and Administration
Calaspargase pegol - mknl (Asparlas) is available as 3,750 units/5 mL (750 units/mL ) in single-dose vial for intravenous infusion.
Acute lymphoblastic leukemia
Recommended dosage: 2,500 units/m
2 intravenously no more frequently than every 21 days.
Source: Servier Pharmaceutics, 2021