Calaspargase Pegol-mknl (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

   Acute Lymphoblastic Leukemia/Lymphoma

   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, investigational, or unproven.

2. Continuation of Therapy

   Aetna considers continued calaspargase pegol - mknl (Asparlas) therapy medically necessary for an indication listed in the Criteria for Initial Approval section 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, 2023

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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 in pediatric and young adult patients age 1 month to 21 years.

Compendial Uses

• Lymphoblastic lymphoma (managed in the same manner as ALL)

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 prescribing information, warnings and precautions include:

• Hypersensitivity: Grade 3 and 4 hypersensitivity 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 with 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