Risk-Adapted Preemptive Tocilizumab to Prevent Severe Cytokine Release Syndrome After CTL019 for Pediatric B-Cell Acute Lymphoblastic Leukemia: A Prospective Clinical Trial.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE: To prospectively evaluate the effectiveness of risk-adapted preemptive tocilizumab (PT) administration in preventing severe cytokine release syndrome (CRS) after CTL019, a CD19 chimeric antigen receptor T-cell therapy.
METHODS: Children and young adults with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukemia were assigned to high- (≥ 40%) or low- (< 40%) tumor burden cohorts (HTBC or LTBC) based on a bone marrow aspirate or biopsy before infusion. HTBC patients received a single dose of tocilizumab (8-12 mg/kg) after development of high, persistent fevers. LTBC patients received standard CRS management. The primary end point was the frequency of grade 4 CRS (Penn scale), with an observed rate of ≤ 5 of 15 patients in the HTBC pre-defined as clinically meaningful. In post hoc analyses, the HTBC was compared with a historical cohort of high-tumor burden patients from the initial phase I CTL019 trial.
RESULTS: The primary end point was met. Seventy patients were infused with CTL019, 15 in the HTBC and 55 in the LTBC. All HTBC patients received the PT intervention. The incidence of grade 4 CRS was 27% (95% CI, 8 to 55) in the HTBC and 3.6% (95% CI, 0.4 to 13) in the LTBC. The best overall response rate was 87% in the HTBC and 100% in the LTBC. Initial CTL019 expansion was greater in the HTBC than the LTBC (
CONCLUSION: Risk-adapted PT administration resulted in a decrease in the expected incidence of grade 4 CRS, meeting the study end point, without adversely impacting the antitumor efficacy or safety of CTL019.
Adolescent, Adult, Antibodies, Monoclonal, Humanized, Antigens, CD19, Child, Child, Preschool, Cytokine Release Syndrome, Drug Resistance, Neoplasm, Female, Follow-Up Studies, Humans, Immunotherapy, Adoptive, Infant, Male, Neoplasm Recurrence, Local, Pilot Projects, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, Prospective Studies, Retrospective Studies, Risk Factors, Salvage Therapy, Survival Rate, Young Adult
Kadauke, S., Myers, R., Li, Y., Aplenc, R., Baniewicz, D., Barrett, D., Barz Leahy, A., Callahan, C., Dolan, J., Fitzgerald, J., Gladney, W., Lacey, S., Liu, H., Maude, S., McGuire, R., Motley, L., Teachey, D., Wertheim, G., Wray, L., DiNofia, A., & Grupp, S. (2021). Risk-Adapted Preemptive Tocilizumab to Prevent Severe Cytokine Release Syndrome After CTL019 for Pediatric B-Cell Acute Lymphoblastic Leukemia: A Prospective Clinical Trial.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 39 (8), 920-930. https://doi.org/10.1200/JCO.20.02477