In a phase III trial (DFCI 11-001) reported in the Journal of Clinical Oncology, Vrooman et al found that the novel pegylated asparaginase formulation calaspargase pegol (calaspargase) given every 3 weeks was associated with similar serum asparaginase activity nadir values, survival outcomes, and toxicities vs standard-formulation pegaspargase given every 2 weeks in pediatric patients with newly diagnosed acute lymphoblastic leukemia (ALL).
Calaspargase contains a linker that differs from that in pegaspargase, resulting in a more hydrolytically stable formulation with a longer half-life.
Study Details
In the multicenter trial, 239 eligible patients aged 1 to ≤ 21 years with ALL (n = 230) or lymphoblastic lymphoma (n = 9) were randomly assigned between June 2012 and June 2015 to receive calaspargase (n = 119) or pegaspargase (n = 120) at 2,500 IU/m2/dose. Beginning at 7 weeks after a single induction dose, calaspargase was given every 3 weeks for 10 doses, and pegaspargase was given every 2 weeks for 15 doses (30 weeks). A total of 87% of patients in each group had B-cell ALL (B-ALL). Serum asparaginase activity was measured at 4, 11, 18, and 25 days after the induction dose and before each postinduction dose, with a level of ≥ 0.1 IU/mL considered therapeutic.
Every 3-week calaspargase had similar nadir serum asparaginase activity, toxicity, and survival outcomes compared with every 2-week pegaspargase. The high nadir serum asparaginase activity observed for both preparations suggest dosing strategies can be further optimized.— Vrooman et al
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Key Findings
Serum asparaginase activity ≥ 0.1 IU/mL was found in > 95% of both treatment groups at 4, 11, and 18 days after the induction dose, and in 88% of the calaspargase vs 17% of the pegaspargase group at day 25 (P < .001). Median serum asparaginase activity at day 25 was 0.319 IU/mL vs 0.056 IU/mL (P < .001).
Median nadir serum asparaginase activity values prior to postinduction doses at 7, 13, 19, and 25 weeks were ≥ 1.0 IU/mL in both groups. Two patients in the calaspargase group had silent inactivation, with all other evaluable patients having nadir serum asparaginase activity ≥ 0.1 IU/mL, and the majority having nadir serum asparaginase activity ≥ 1.0 IU/mL throughout 30 weeks.
Among 230 evaluable patients, complete remission was achieved in 109 (95%) of 115 in the calaspargase group vs 114 (99%) of 115 in the pegaspargase group (P = .12). Among patients with B-ALL and evaluable minimal residual disease (MRD), high end-induction MRD was found in 10% vs 11% of patients (P = .99).
At a median follow-up of 5.3 years, 5-year event-free survival was 88.1% vs 84.9% (P = .65).
The frequency of postinduction asparaginase-related toxicities was 38% vs 38%, with no difference in rates of grade ≥ 2 allergy (17% vs 14%), grade ≥ 2 pancreatitis (13% vs 15%), grade ≥ 2 thrombosis (14% vs 12%), bleeding events (1% vs 0%), or grade ≥ 4 hyperbilirubinemia (3% vs 3%).
The investigators concluded, “Every 3-week calaspargase had similar nadir serum asparaginase activity, toxicity, and survival outcomes compared with every 2-week pegaspargase. The high nadir serum asparaginase activity observed for both preparations suggest dosing strategies can be further optimized.”
Lynda M. Vrooman, MD, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Sigma-Tau Pharmaceuticals and Baxalta/Shire. For full disclosures of the study authors, visit ascopubs.org.
