Discontinuation of Asparaginase Impacts Event-Free Survival in Patients with ALL

Asparaginase is often included as part of treatment for acute lymphocytic leukemia (ALL) but is associated with toxicities that may result in discontinuation. Erwinia asparaginase is often substituted for allergic reactions. The majority of treatment protocols use discrete, discontinuous periods of asparagine depletion, and the impact of Erwinia asparaginase substitution or complete asparaginase discontinuation is unknown.

In a study presented at the 2019 ASCO Annual Meeting, researchers found that discontinuation of asparaginase doses is associated with significantly inferior event-free survival (EFS).

The study included patients aged 1 to 30.99 years who were enrolled in frontline Children’s Oncology Group trials for B-cell ALL, including patients with standard- (n = 5,195) and high-risk (n = 3,001) disease. The number of prescribed pegaspargase doses varied by trial, risk strata, and randomization. Maintenance therapy did not contain asparaginase.

The researchers assessed EFS between those receiving all prescribed doses of pegasparagase and those who switched to Erwinia asparaginase and received all doses versus those who did not receive all asparaginase doses.

The cumulative incidence of pegasparagase discontinuation was 12.2% (standard deviation [SD] = 4.6%) for standard-risk patients and 25.4% (SD = 0.8%) for high-risk patients.

After adjusting for patient and disease variables, high-risk patients who did not receive all prescribed asparaginase doses had inferior EFS (hazard ratio [HR] = 1.5; 95% confidence interval [CI], 1.2-1.9; P = 0.002] compared with those who received all pegasparagase doses.

Patients who substituted with Erwinia asparaginase and completed all doses were not at increased risk (HR = 1.1; 95% CI, 0.7-1.6; P = 0.69). When researchers included patients who discontinued asparaginase due to pancreatitis or thrombosis, they observed similar results.

Standard-risk patients who discontinued asparaginase were not at an increased risk (HR = 1.2; 95% CI, 0.9-1.6; P = 0.23), except when analyses only included patients with slow early response (HR = 1.7; 95% CI, 1.1-2.7; P = 0.03).

Seidler M, Dontchos BN, Mercaldo S, et al. Impact of asparaginase discontinuation on outcome in childhood ALL: A report from the Children’s Oncology Group (COG).