The U.S. Food and Drug Administration (FDA) has approved calaspargase pegol-mknl (Asparlas) as a component of a multi-agent chemotherapeutic regimen to treat acute lymphoblastic leukemia (ALL) in pediatric and young adult patients age 1 month to 21 years.
Calaspargase pegol-mknl is an asparagine-specific enzyme intended to provide a longer interval between doses compared to other available pegaspargase products.
The recommended dosage of calaspargase pegol-mknl is 2,500 U/m2 given no more frequently than every 21 days.
The FDA said it approved calaspargase pegol-mknl because the drug maintained nadir serum asparaginase activity above the level of 0.1 U/mL when given at 2,500 U/m2 every 3 weeks.
Calaspargase pegol-mknl was evaluated in Study DFCI 11-001, a trial of 237 children and adolescents with newly diagnosed ALL or lymphoblastic lymphoma. The patients’ median age was 5 years (range, 1 to 20 years).
They received calaspargase pegol-mknl at 2,500 U/m2 (n=118) or pegaspargase at 2,500 U/m2 (n=119) as part of a Dana-Farber Cancer Institute (DFCI) ALL Consortium backbone therapy.
The median duration of exposure was 8 months for both calaspargase pegol-mknl and pegaspargase.
Among the patients with B-cell lineage ALL, the complete remission rate was 98% in the calaspargase pegol-mknl arm and 99% in the pegaspargase arm. Estimated overall survival rates were comparable between the arms.
Common grade 3 or higher adverse events (in the calaspargase pegol-mknl and pegaspargase arms, respectively) included elevated transaminase (52% and 66%), bilirubin increase (20% and 25%), pancreatitis (18% and 24%), and abnormal clotting studies (14% and 21%).
There was one fatal adverse event among patients on calaspargase pegol-mknl—multi-organ failure in the setting of chronic pancreatitis associated with a pancreatic pseudocyst.
The safety of calaspargase pegol-mknl was also evaluated in Study AALL07P4, a trial of patients with newly diagnosed, high-risk B-precursor ALL.
The patients received calaspargase pegol-mknl at 2,500 U/m2 (n=43) or 2,100 U/m2 (n=68) or pegaspargase at 2,500 U/m2 (n=52) as a component of an augmented Berlin-Frankfurt-Münster regimen.
The patients’ median age was 11 years (range, 1 to 26 years). The median duration of exposure was 7 months for both calaspargase pegol-mknl and pegaspargase.
There were three induction deaths among the 111 patients who received calaspargase pegol-mknl (2.8%) but no induction deaths among the 52 patients treated with pegaspargase.
Additional details on these studies and calaspargase pegol-mknl can be found in the drug’s prescribing information.
Calaspargase pegol-mknl is a product of Servier Pharmaceuticals LLC.