Asparaginase discontinuation linked to inferior EFS in acute lymphoblastic leukemia

Sumit Gupta

CHICAGO — Discontinuation of asparaginase appears associated with significantly inferior EFS among patients with acute lymphoblastic leukemia compared with those who stayed on the treatment or substituted it with asparaginase Erwinia chrysanthemi, according to results of a study presented at ASCO Annual Meeting.

“Our results provide reassurance that substituting asparaginase with Erwinia does not impact leukemia outcomes,” Sumit Gupta, MD, PhD, oncologist and clinical investigator at The Hospital for Sick Children and associate professor in the department of pediatrics at University of Toronto, said during the presentation. “Asparaginase should only be discontinued when the risk of continuing it outweighs the increased risk of relapse, particularly in higher risk patients.”

Asparaginase (ASP) is an important part of treatment for ALL. However, it is often discontinued because of toxicity. Patients who have an allergic reaction, but no other toxicities, usually switch to asparaginase Erwinia chrysanthemi (Erwinaze; Jazz Pharmaceuticals).

Many treatment protocols use discrete discontinuous periods of ASP depletion. However, the impact of asparaginase Erwinia chrysanthemi (EA) substitution or complete discontinuation on outcomes is unknown.

Gupta and colleagues analyzed 5,195 standard-risk and 3,001 high-risk patients (age range, 1-30.99 years) enrolled in frontline Children’s Oncology Group trials for B-cell ALL.

The number of pegaspargase doses prescribed varied in each trial based on risk strata and randomization. Maintenance therapy did not include ASP.

The researchers analyzed the patients starting at maintenance therapy and compared EFS among those receiving all prescribed doses of pegaspargase, those who switched to EA but still received all doses, and those who did not receive all ASP doses.

Incidence of pegaspargase discontinuation was 12.2% (± 4.6%) among patients with standard-risk ALL and 25.4% (± 0.8%) among patients with high-risk ALL.

Results of multivariable analyses showed that high-risk patients who did not receive all prescribed ASP doses had inferior EFS compared with patients who received all prescribed pegaspargase doses (HR = 1.5; 95% CI, 1.2-1.9).

Patients who substituted ASP with EA but also completed all prescribed doses were not at an increased risk compared with patients who stayed on ASP (HR = 1.1; 95% CI, 0.7-1.6).

Standard-risk patients who discontinued ASP did not demonstrate an elevated risk (HR = 1.2; 95% CI, 0.9-1.6) unless the analyses were restricted to standard-risk patients with slow early response (HR = 1.7; 95% CI, 1.1-2.7).

Gupta added that making sure the global shortage of Erwinia is remedied will be critical moving forward.

“Efforts to restore the global Erwinia supply and prevent future disruptions are important to maintaining patient outcomes,” Gupta said. “Future studies should look at the impact of asparaginase discontinuation in T-lineage disease, as well as determine whether there is a safe [dosage] for this population.” – by John DeRosier

Reference:

Gupta S, et al. Abstract 10005. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosures: Gupta reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.