Continuous PEGasparaginase dosing regimen decreases hypersensitivity reactions in children with acute lymphoblastic leukemia

A recent study showed that a continuous dosing regimen of PEGasparaginase (PEGasp) can effectively prevent the formation of antibody and reduce the risk of hypersensitivity reactions. These findings were published in the Journal of Clinical Oncology. 
Patients diagnosed with Acute Lymphoblastic Leukemia (ALL) were included in the DCOG ALL11 protocol. These patients were administered PEGasp as part of their treatment. Out of 818 patients, 312 were categorized as medium-risk and were randomized to receive 14 individualized doses of PEGasp. The administration of these doses occurred once every two weeks, following either a non-continuous or continuous schedule after the initial three doses during the induction phase. The primary objective of this study was to assess whether the continuous dosing schedule, without any asparaginase-free interval, would lead to a lower occurrence of hypersensitivity reactions to PEGasp compared to the standard non-continuous dosing schedule. The secondary endpoints of the study included evaluating other asparaginase-related toxicities, asparaginase activity and antibody levels, as well as overall treatment outcome.
In the induction phase, hypersensitivity reactions were detected in 27 out of 818 patients. Following random assignment assignment of 312 medium risk patients, 4 out of 155 (2.6%) patients in the continuous treatment arm and 17 out of 157 (10.8%) patients in the noncontinuous treatment arm reported hypersensitivity reactions. Among these reactions, 2 versus 13 were inactivating reactions. In the continuous treatment arm, the occurrence of inactivating hypersensitivity reactions was 7 times lower. Additionally, antibody levels were notably reduced in the continuous treatment arm. There were no notable differences in the total number of asparaginase-related toxicities between the two treatment groups, besides a lower incidence of elevated amylase in the continuous treatment group. 
As a result, a continuous PEGasp dosing schedule is successful in preventing antibody formation neutralizing and hypersensitivity responses. This continuous schedule demonstrated no rise in toxicity levels and had no impact on the efficacy.