Phase 2 multicenter study of pegaspargase in Japanese patients with previously untreated acute lymphoblastic leukemia

TL;DR

This study evaluated the safety and effectiveness of pegaspargase in Japanese patients with newly diagnosed acute lymphoblastic leukemia.

Contribution

The study provides new evidence on the tolerability and pharmacokinetics of lyophilized pegaspargase in the Japanese population.

Findings

All 26 patients experienced at least one treatment-emergent adverse event, including decreases in blood fibrinogen and platelet count.

Plasma asparaginase activity reached and was maintained at ≥ 0.1 IU/ml for 14 days in all evaluable patients.

No deaths were reported, indicating that lyophilized pegaspargase is a well-tolerated treatment option for Japanese ALL patients.

Abstract

Pegaspargase is a pegylated formulation of E. coli-derived asparaginase, which when combined with multi-agent chemotherapy is an effective, well-established therapy for acute lymphoblastic leukemia (ALL). This study evaluated the efficacy, safety and pharmacokinetics of lyophilized pegaspargase in the Japanese population. The study had two parts; the primary endpoint for Part 1 was the incidence and nature of treatment-emergent adverse events (TEAEs), including those related to pegaspargase, to determine the number of patients who experience intolerable toxicity during a tolerability assessment period. The primary endpoint for Part 2 was the percentage of patients with plasma asparaginase activity of ≥ 0.1 IU/ml 14 days after administration of the first dose of lyophilized pegaspargase. All 26 patients included in the safety analysis experienced at least one TEAE. Frequently reported TEAEs related to lyophilized pegaspargase included decreases in blood fibrinogen, antithrombin III, white blood cell count, and platelet count. No deaths were reported. Plasma asparaginase activity reached ≥ 0.1 IU/ml 5 min after the first dose of lyophilized pegaspargase and was maintained for 14 days in all patients with evaluable samples. The results of this study show that lyophilized pegaspargase represents an effective and well-tolerated first-line treatment option in Japanese patients with ALL.

The online version contains supplementary material available at 10.1007/s12185-025-03976-4.

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