Calaspargase and Pegaspargase Elicit Similar Responses, Toxicity Profiles in Pediatric and Adolescent ALL

Pediatric and adolescent patients with acute lymphoblastic leukemia experienced similar outcomes when treated with either calaspargase pegol or pegaspargase.

Calaspargase pegol (Asparlas) and pegaspargase yielded comparable results in terms of responses, activity, and safety in the treatment of pediatric and adolescent patients with newly diagnosed acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma, according to the results of a phase 3 trial (NCT01574274) published in the Journal of Clinical Oncology.

Of the evaluable patients who were included on the study (n = 239), 99% of those who were treated with pegaspargase and 95% of those who were treated with calaspargase achieved a complete response (P = .12). Investigators did not identify a significant difference in frequency of high end–induction minimal residual disease between cohorts of patients with B-cell ALL (pegaspargase, 11%; Calaspargase, 10%; P = .99). After a median follow-up of 5.3 years, the 2 drugs yielded event-free survival rates of 84.9% and 88.1%, respectively (P = .65), as well as a 5-year overall survival rate of 95.8% and 94.0%, respectively (P = .72).

“Our results suggest that calaspargase may feasibly be used during induction therapy, without excess toxicity or significant impact on end-induction response,” wrote the investigators. “Given its longer half-life, calaspargase can be dosed less frequently than pegaspargase, especially in regimens that aim to achieve prolonged asparagine depletion.”

Those who enrolled were randomized to receive intravenous pegaspargase (n = 120) or calaspargase (n = 119) at 2500 IU/m2 per dose, with patient received 1 induction dose. At week 7, pegaspargase was given to patients every other week for 15 doses and calaspargase was given every 3 weeks for 10 doses. Serum asparaginase activity (SAA) was assessed by investigators on days 4, 11, 18, and 25 following the induction dose and prior to the postinduction dose.

Patients included in the study were between the ages of 1 to 21 years old with newly diagnosed disease. Most patients had ALL (n = 230) with a minority of patients presenting with lymphoblastic lymphoma (n = 9).Patients had a median age of 5.2 years (range, 1.0-20.9).

Additional findings from the study indicated that, following the induction dose, SAA was 0.1 IU/mL or greater in over 95% of patients across both arms 18 days after dosing. However, 88% of patients in the calaspargase arm had an SAA of 0.1 IU/mL or more versus only 17% in the pegaspargase arm by day 25 (P <.001). It was also found that the median nadir SAAs were comparable postinduction in both groups of patients.

Reference

Vrooman LM, Blonquist TM, Stevenson KE, et al. Efficacy and toxicity of pegaspargase and calaspargase pegol in childhood acute lymphoblastic leukemia: results of DFCI 11-001. J Clin Oncol. Published online July 6, 2021. doi:10.1200/JCO.20.03692