A Comprehensive Analysis of Adverse Events in the First 30 Days of Phase 1 Pediatric CAR T-Cell Trials

Authors

Sara K. Silbert, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, United States.
Sanna Madan, National Cancer Institute, Bethesda, Maryland, United States.
Elizabeth M. Holland, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, United States.
Seth M. Steinberg, Biostatistics and Data Management Section, National Cancer Institute, NIH, Bethesda, Maryland, United States.
Lauren Little, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, United States.
Toni Foley, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, United States.
Monica Epstein, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, United States.
Angela Sarkisian, George Washington University School of Medicine & Health Sciences, United States.
Daniel W. Lee, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), United States.
Ekaterina Nikitina, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, United States.
Showri Kakumanu, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, United States.
Eytan Ruppin, National Cancer Institute, Bethesda, Maryland, United States.
Haneen Shalabi, National Institutes of Health, Bethesda, Maryland, United States.
Bonnie Yates, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States.
Nirali N. Shah, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, United States.

Document Type

Journal Article

Publication Date

7-24-2023

Journal

Blood advances

DOI

10.1182/bloodadvances.2023009789

Abstract

The tremendous success of chimeric antigen receptor (CAR) T-cells in children and young adults (CAYA) with relapsed/refractory B-cell acute lymphoblastic leukemia is tempered by toxicities such as cytokine release syndrome (CRS). Despite expansive information about CRS, profiling of specific end-organ toxicities secondary to CAR T-cell therapy in CAYAs is limited. This retrospective, single-center study sought to characterize end-organ specific adverse events (AEs) experienced by CAYAs during the first 30 days following CAR T-cell infusion. AEs graded using Common Terminology Criteria for Adverse Events (CTCAE) were collected on 134 patients enrolled on one of three phase 1 CAR T-cell trials (NCT01593696, NCT02315612, and NCT03448393), targeting CD19 and/or CD22. A total of 133 (99.3%) patients experienced at least 1 > grade 3 (Gr3) AE across 17 organ systems, 75 (4.4%) of which were considered dose or treatment limiting toxicities. Excluding cytopenias, 109 (81.3%) patients experienced a median of 3 >Gr3 non-cytopenia (NC) AEs. The incidence of >Gr3 NC AEs was associated with development (p <0.0001) and severity (p=0.0002) of CRS as well as pre-infusion disease burden (> 25% marrow blasts; p <0.0001). While those with complete remission trended toward experiencing more >Gr3 NC AEs than non-responders, (median 4 versus 3, p=0.10), non-responders experiencing CRS (n=17, 37.8%) had the highest degree of NC AEs across all patients (median 7 versus 4 in responders experiencing CRS, p=0.07). Greater understanding of these toxicities and the ability to predict which patients may experience more toxicities is critical as the array of CAR T-cell therapies expand. Clinical Trial # NCT01593696, NCT03448393.

APA Citation

Silbert, Sara K.; Madan, Sanna; Holland, Elizabeth M.; Steinberg, Seth M.; Little, Lauren; Foley, Toni; Epstein, Monica; Sarkisian, Angela; Lee, Daniel W.; Nikitina, Ekaterina; Kakumanu, Showri; Ruppin, Eytan; Shalabi, Haneen; Yates, Bonnie; and Shah, Nirali N., "A Comprehensive Analysis of Adverse Events in the First 30 Days of Phase 1 Pediatric CAR T-Cell Trials" (2023). GW Authored Works. Paper 3038.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3038

Department

School of Medicine and Health Sciences Student Works