SickKids study finds increased risk of leukemia relapse for children who miss doses of certain cancer therapy

There has been a global shortage of Erwinia, a commonly used drug to treat acute lymphoblastic leukemia (ALL), for several years. A research team led by Dr. Sumit Gupta, Staff Oncologist in the Division of Haematology/Oncology, and Associate Scientist in the Child Health Evaluative Sciences program at The Hospital for Sick Children (SickKids), investigated whether missing a dose or multiple doses of this type of therapy increased risk of relapse in children with ALL. 

What problem were you looking to solve with your research?

Children with acute lymphoblastic leukemia (ALL), the most common cancer in kids, have excellent cure rates when treated appropriately. 

One of the main drugs used to treat ALL is called PEG-Asparaginase (PEG). However, some children develop an allergy to PEG; for these kids, we use an alternative version called Erwinia. For the last several years, there has been a global shortage of Erwinia, which has meant that some children who needed Erwinia were not able to receive it. We wanted to know whether missing doses of Asparaginase, either PEG or Erwinia, would impact the chance of curing a child’s leukemia.  

What did you find?

We found that for children who developed an allergy to PEG and switched to Erwinia, their chance at cure was not impacted as long as they got all of the Erwinia doses they needed. However, for children with higher risk ALL, missing entire doses of Asparaginase was associated with a 50 per cent increase in the risk of relapse. 

How did you come to these findings?

We looked at data from over 8,000 children with ALL treated on clinical trials by the Children’s Oncology Group (COG). Thankfully, there were data available from COG on which patients got all of their Asparaginase and which patients missed doses. We also looked at the treatment outcomes of all the participants to determine the likelihood of relapse if a dose or multiple doses were missed. 

What should clinicians take away from this study? What should patients and families take away from this study?

There are a few important messages. The first is that clinicians should only omit Asparaginase when the risk of giving more is greater than the increased risk in relapse that our study showed. There are some situations where this is the case, such as when a patient develops certain severe side effects because of this type of medication. 

However, it also means that missing these doses because of drug shortages should be considered unacceptable. Because the shortage is global in nature, there is very little any individual clinician or even institution can do. Governments, clinicians and families all need to work together to find a solution. 

Finally, it also shows more broadly the impact of cancer drug shortages. In the COVID-19 era, when drug supply chains may be at risk, we need to carefully monitor our drug supplies to ensure our patients continue to have access. 

What are your next steps? 

We are going to try to determine whether there is a “safe” number of PEG or Erwinia doses you can miss, which may differ between different subtypes of ALL. As a community, our most important next step must be to ensure that current drug shortages are solved and prevented from happening again. 

This study was supported by the National Cancer Institute and SickKids Foundation.