iMATRIX

Summary

Checkpoint inhibitors in children with solid tumors

This study examined whether immunotherapy with the drug atezolizumab is a safe and effective treatment for children with a recurrent or difficult-to-treat solid tumor or lymphoma. Researchers at the Princess Máxima Center, led by Prof. Dr. Michel Zwaan, conducted this study together with the European consortium ITCC (Innovative Therapies for Children with Cancer).

Research on atezolizumab in children

In about 9% of children with a solid tumor (such as neuroblastoma) or lymphoma, the protein PD-L1 is present on the tumor cells. This protein helps tumor cells evade the immune system. The drug atezolizumab, a so-called checkpoint inhibitor, blocks the PD-L1 protein. As a result, the immune system can once again recognize and destroy the tumor cells.

This study investigated the safety and effectiveness of atezolizumab in children with a solid tumor or lymphoma whose disease had returned (relapsed) or did not respond sufficiently to previous treatments (refractory), and whose tumors expressed the PD-L1 protein.

What were the results?

Treatment with atezolizumab was generally well tolerated. Children did experience side effects, such as fever and fatigue, but these were usually manageable.

However, the effect of the drug was limited. Only a small number of children showed a response in their tumor. Other studies with different checkpoint inhibitors (nivolumab and pembrolizumab) have also shown limited effect in children with solid tumors.

There are several possible explanations for this:
• Pediatric tumors may contain fewer targets that immune cells can recognize.
• Different checkpoint proteins may play a role in pediatric tumors than in adult tumors.

Checkpoint inhibitors do appear to be effective in two specific groups of pediatric tumors: Hodgkin lymphoma and tumors with a high number of genetic abnormalities. The latter may occur in children with an underlying problem in the DNA repair system, but it may also be present only in the tumor.

Would you like to read the scientific publication? Please look here: Geoerger B, et al. Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. Lancet Oncol. 2020 Jan;21(1):134-144.