In a Dutch study reported in the Journal of Clinical Oncology, van der Sluis et al found that continuous dosing of PEGasparaginase was associated with a significantly reduced incidence of hypersensitivity reactions vs standard noncontinuous dosing in newly diagnosed pediatric patients with medium-risk acute lymphoblastic leukemia (ALL).
Study Details
In the multicenter open-label trial, 818 patients aged 1 to 18 years received PEGasparaginase treatment. A total of 312 patients with medium-risk disease were randomly assigned to receive 14 individualized PEGasparaginase doses once every 2 weeks in a continuous schedule (n =155) or in a noncontinuous schedule (n =157) after 3 doses during induction. In the continuous schedule, dosing continued with no break after the 3 induction doses; in the noncontinuous schedule, patients began the 14-dose regimen at the beginning of intensification, with a 3-month treatment-free interval after the 3 induction doses. The primary outcome measure was hypersensitivity reactions, defined as allergies, allergic-like reactions, and silent inactivation.
Key Findings
Among all 818 patients, 27 (3.3%) had hypersensitivity reactions during induction.
Among the randomly assigned population of medium-risk patients, hypersensitivity reactions occurred in 4 (2.6%) of 155 patients in the continuous treatment group vs 17 (10.8%) of 157 in the noncontinuous treatment group (P < .01). Inactivating reactions were observed in 2 (1.3%) vs 13 patients (8.3%; odds ratio = 0.15, 95% confidence interval = 0.03–0.65, P < .01). Antibody levels were significantly lower in the continuous arm (P < .01).
Apart from a higher incidence of increased amylase in the noncontinuous group (14.6% vs 16.5%, P < .05), there were no significant differences in any other any-grade asparaginase-associated toxicities between groups. Timing of onset of toxicities was associated with timing of PEGasparaginase doses.
No significant differences between the noncontinuous treatment group vs the continuous treatment group were found for 5-year cumulative incidence of relapse (4.0% vs 5.6%), 5-year cumulative incidence of death in first remission (0.6% vs 1.9%), or 5-year disease-free survival (95.3% vs 91.9%).
The investigators concluded, “A continuous dosing schedule of PEGasparaginase is an effective approach to prevent antibody formation and inactivating hypersensitivity reactions. The continuous PEGasparaginase schedule did not increase toxicity and did not affect the efficacy of the therapy.”
Inge M. van der Sluis, MD, PhD, of the Princess Máxima Center for Pediatric Oncology, Utrecht, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by medac GmbH and Jazz Pharmaceuticals. For full disclosures of the study authors, visit ascopubs.org.
