Abstract
Although survival for many pediatric cancers has improved with advances in conventional chemotherapeutic regimens and surgical techniques in the last several decades, it remains a leading cause of disease-related death in children. Outcomes in patients with recurrent, refractory, or metastatic disease are especially poor. Recently, the advent of alternative classes of therapies, including immunotherapies, have revolutionized systemic treatment for pediatric malignancies. Several classes of immunotherapies, including chimeric antigen receptor (CAR) T cell therapy, transgenic T-cell receptor (TCR)-T cell therapy, bispecific T-cell engagers, and monoclonal antibody checkpoint inhibitors have been FDA-approved or entered early-phase clinical trials in children and young adults. The pediatric surgeon is likely to encounter these therapies during the care of children with malignancies and should be familiar with the classes of therapy, indications, adverse events, and potential need for surgical intervention in these cases. This review from the APSA Cancer Committee offers a brief discussion of the three most encountered classes of immunotherapy in children and young adults and discusses surgical relevance. Level of Evidence: IV.
| Original language | English |
|---|---|
| Pages (from-to) | 2119-2127 |
| Number of pages | 9 |
| Journal | Journal of Pediatric Surgery |
| Volume | 58 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2023 |
Bibliographical note
Publisher Copyright:© 2023 Elsevier Inc.
Funding
Current consensus grading of CRS is summarized in Table 1. Mild to moderate CRS is treated with supportive care, including hospitalization, broad spectrum antibiotics, pain relief, respiratory support, and vasopressors as necessary [24]. Severe (grade 3 or greater) CRS has been reported in up to 25% of pediatric patients in large series [ 18–20,25]. Of note, clinical trials have reported fewer cases of severe CRS over time. This may indicate earlier recognition of potentially severe cases and earlier treatment, or overall increasing experience with CAR dosing and protocols.Perhaps most familiar to pediatric surgeons is Dinutuximab (Unituxin®), an anti-GD2 antibody which induces cell-mediated and complement-dependent cytotoxicity against GD2-expressing tumor cells including neuroblastoma. Starting in the mid-1980s, preclinical studies and early phase clinical trials demonstrated near-uniform expression of GD2 on neuroblastoma cells and evidence for improved outcomes in patients after dinutuximab treatment [74,75]. ANBL0032 (NCT00026312), a randomized phase III trial performed through the Children's Oncology Group, demonstrated significantly improved event-free survival (56.6% vs 46.1%) and overall survival (73.2% vs 56.6%) in children with high-risk neuroblastoma receiving dinutuximab during consolidation therapy versus isoretinoin alone [76], and ANBL0931 (NCT01041638) subsequently provided follow-up safety and toxicity data and supported the conclusions of the earlier report [77]. Early regimens included coadministration of IL2, but toxicities due to this agent frequently led to treatment cessation, and a multi-institution international trial demonstrated no difference in outcomes between children receiving dinutuximab with and without IL2 adminstration [48]. It has therefore been removed from current protocols. Dinutuximab is now part of post-consolidation therapy in all treatment arms of the current high risk neuroblastoma study (ANBL1531; NCT03126916). In addition, based on growing evidence that induction-phase dinutuximab administration may significantly improve outcomes for high-risk neuroblastoma patients [78], the current COG trial ANBL1821 (NCT03794349) will evaluate upfront dinutuximab in relapsed, refractory, or progressive neuroblastoma.
| Funders | Funder number |
|---|---|
| Children’s Oncology Group | ANBL1531, NCT03126916, ANBL1821, ANBL0931, NCT01041638, NCT03794349 |
Keywords
- BiTE
- Cancer
- CAR T cell
- Checkpoint inhibitor
- Immunotherapy
- Transgenic TCR-T cell
ASJC Scopus subject areas
- Surgery
- Pediatrics, Perinatology, and Child Health
