Calaspargase pegol (Asparlas)

Number: 0957

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses calaspargase pegol (Asparlas) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

1. 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:
   
   
   1. The requested medication will be used in conjunction with multi-agent chemotherapy; and
   2. The member is 21 years of age or younger.

   Aetna considers all other indications as experimental and investigational.

2. 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/m² intravenously no more frequently than every 21 days.

Source: Servier Pharmaceutics, 2021

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :
Other CPT codes related to the CPB:
96413 - 96415	Chemotherapy administration, intravenous infusion technique
HCPCS codes covered if selection criteria are met:
Calaspargase pegol (Asparlas) - no specific code:
ICD-10 codes covered if selection criteria are met:
C83.50 - C83.59	Lymphoblastic (diffuse) lymphoma
C91.00 - C91.02	Acute lymphoblastic leukemia

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Background

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/m² 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.

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References