Immunotherapy Associated Neurotoxicity in Pediatric Oncology.

Haneen Shalabi,Anandani Nellan,Nirali N Shah,Juliane Gust

doi:10.3389/fonc.2022.836452

Abstract

Novel immunotherapies are increasingly being employed in pediatric oncology, both in the upfront and relapsed/refractory settings. Through various mechanisms of action, engagement and activation of the immune system can cause both generalized and disease site-specific inflammation, leading to immune-related adverse events (irAEs). One of the most worrisome irAEs is that of neurotoxicity. This can present as a large spectrum of neurological toxicities, including confusion, aphasia, neuropathies, seizures, and/or death, with variable onset and severity. Earlier identification and treatment, generally with corticosteroids, remains the mainstay of neurotoxicity management to optimize patient outcomes. The pathophysiology of neurotoxicity varies across the different therapeutic strategies and remains to be elucidated in most cases. Furthermore, little is known about long-term neurologic sequelae. This review will focus on neurotoxicity seen with the most common immunotherapies used in pediatric oncology, including CAR T cell therapy, alternative forms of adoptive cell therapy, antibody therapies, immune checkpoint inhibitors, and tumor vaccines. Herein we will discuss the incidence, pathophysiology, symptomatology, diagnosis, and management strategies currently being utilized for immunotherapy-associated neurotoxicity with a focus on pediatric specific considerations.

Highlights

The rapid emergence of novel immunotherapies has dramatically shifted the treatment paradigm in oncology, in those with relapsed/refractory disease where standard therapies have failed
The majority of events resolve with a short interruption in the infusion, dose de-escalation, or complete discontinuation of therapy, and corticosteroids can be used in the presence of severe neurotoxicity
Use of these antibodies in pediatric hematologic malignancies has shown an incidence of neurotoxicity of up to 30% in published trials, with the most common neurologic adverse events being pain, peripheral neuropathy, and headache [151,152,153,154]

Summary

INTRODUCTION

The rapid emergence of novel immunotherapies has dramatically shifted the treatment paradigm in oncology, in those with relapsed/refractory disease where standard therapies have failed. The Cornell Assessment of Pediatric Delirium (CAPD), was validated for recognizing delirium in children hospitalized in intensive care units [16] This tool has been adopted into the guidelines for neurotoxicity monitoring after CAR T cell therapy and is commonly used in settings where it has not yet been validated, such as acute care units and even outpatient care [15]. A custom caregiver checklist was developed to monitor pediatric and young adult patients for neurotoxicity in the acute setting post-CAR T cell therapy [17]. Dysarthria 8-12% Headache 22-42% Insomnia 21% Myalgia 19% Myasthenia 13-15% Pain (grade 3/4) 8% Voice disorder 5-13%

References for Pediatric Studies

K27M targeted peptide vaccine

SUMMARY