Calaspargase pegol (Asparlas)

Number: 0957

Policy

Aetna considers calaspargase pegol - mknl (Asparlas) medically necessary for the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma when both 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 continued treatment with calaspargase pegol - mknl medically necessary in members requesting reauthorization for a medically necessary indication who have not experienced disease progression or an unacceptable toxicity while on the current regimen.

Aetna considers calaspargase pegol - mknl experimental and investigational for all other indications because its effectiveness for other indications has not been established.

Dosing Recommendations

Recommended dosage: 2,500 units/m2 intravenously no more frequently than every 21 days.

Source: Prescribing Information. Asparlas. Servier Pharmaceuticals LLC, 2018.

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 (Asparlas) 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. 

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.

Dosing Adjustments

Monitor patients at least weekly, with bilirubin, transaminases, glucose and clinical examinations until recovery from the cycle of therapy. If an adverse reaction should occur, modify treatment according to the following, where Grade 1 is mild, grade 2 is moderate, grade 3 is severe, and grade 4 is life-threatening: 

Infusion Reaction or Hypersensitivity Reaction

• Grade 1: Reduce the infusion rate by 50%
• Grade 2: Interrupt the infusion of Asparlas; Treat the symptoms; When symptoms resolve, resume the infusion and reduce the infusion rate by 50%
• Grade 3 to 4: Discontinue Asparlas permanently

Hemorrhage

• Grade 3 to 4: Hold Asparlas; Evaluate for coagulopathy and consider clotting factor replacement as needed; Resume Asparlas with the next scheduled dose if bleeding is controlled.

Pancreatitis

• Grade 3 to 4: Hold Asparlas for elevations in lipase or amylase >3 times the ULN until enzyme levels stabilize or are declining; Discontinue Asparlas.

Thromboembolism

• Uncomplicated deep vein thrombosis: Hold Asparlas ; Treat with appropriate antithrombotic therapy; Upon resolution of symptoms consider resuming Asparlas, while continuing antithrombotic therapy.
• Severe or life-threatening thrombosis: Discontinue Asparlas permanently; Treat with appropriate antithrombotic therapy.

Hepatotoxicity

• Total bilirubin more than 3 times to no more than 10 times the upper limit of normal: Hold Asparlas until Total bilirubin levels go down to ≤ 1.5 times the upper limit of normal
• Total bilirubin more than 10 times the upper limit of normal: Discontinue Asparlas and do not make up for missed doses upper limit of normal.

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

The above policy is based on the following references: