Calaspargase and pegaspargase produced similar outcomes in children and adolescents with newly diagnosed acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL), according to a phase 3 trial published in the Journal of Clinical Oncology.
Calaspargase and pegaspargase produced similar nadir serum asparaginase activity (SAA), toxicity, response, and survival outcomes.
The phase 3 trial (ClinicalTrials.gov Identifier: NCT01574274) included 239 patients — 230 with ALL and 9 with LL. The patients’ median age at diagnosis was 5.2 years (range, 1.0-20.9 years).
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Patients were randomly assigned to receive pegaspargase (n=120) or calaspargase (n=119). They received a single dose of either therapy on day 7 of induction. Starting at week 7, pegaspargase was given every 2 weeks (15 total doses), and calaspargase was given every 3 weeks (10 total doses) for 30 consecutive weeks.
At 18 days after the induction dose, SAA levels were 0.1 IU/mL or greater in at least 95% of patients in both arms.
On day 25, 88% of patients in the calaspargase arm had SAA levels of 0.1 IU/mL or greater, compared with 17% of patients in the pegaspargase arm (P ˂.001). The median SAA was higher with calaspargase than with pegaspargase — 0.319 IU/mL and 0.056 IU/mL, respectively (P <.001).
At 7 weeks or later after starting postinduction asparaginase, the median nadir SAA levels were similar between the treatment arms.
There were 230 patients evaluable for induction events. The complete response rate was 95% in the calaspargase arm and 99% in the pegaspargase arm (P =.12).
Among evaluable patients with B-ALL, there was no significant difference between the arms with regard to frequency of high end-induction minimal residual disease — 10% with calaspargase and 11% with pegaspargase (P =.99).
There were no significant differences between the treatment arms in frequencies of asparaginase allergy, pancreatitis, thrombosis, or hyperbilirubinemia during induction or postinduction phases.
The 5-year event-free survival rate was 84.9% with pegaspargase and 88.1% with calaspargase (P =.65). The 5-year overall survival rate was 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,” the study authors wrote. “Given its longer half-life, calaspargase can be dosed less frequently than pegaspargase, especially in regimens that aim to achieve prolonged asparagine depletion.”
Based on the findings of the high nadir SAA levels for both preparations, the authors suggested that the dosing strategies can be further optimized.
Disclosures: This research was supported by Sigma-Tau Pharmaceuticals and Baxalta/Shire. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
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
