Risk-Adapted Preemptive Tocilizumab to Prevent Severe Cytokine Release Syndrome After CTL019 for Pediatric B-Cell Acute Lymphoblastic Leukemia: A Prospective Clinical Trial
| Autor: | Regina McGuire, Julie C. Fitzgerald, Diane Baniewicz, Lisa Wray, Colleen Callahan, Allison Barz Leahy, Whitney L. Gladney, Stephan Kadauke, Regina M. Myers, Joseph G Dolan, Laura S Motley, Hongyan Liu, Yimei Li, David M. Barrett, Gerald Wertheim, Simon F. Lacey, David T. Teachey, Stephan A. Grupp, Richard Aplenc, Shannon L. Maude, Amanda M. DiNofia |
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| Rok vydání: | 2021 |
| Předmět: |
Oncology
Adult Male Cancer Research medicine.medical_specialty Adolescent medicine.medical_treatment Antigens CD19 Salvage therapy Pilot Projects Antibodies Monoclonal Humanized Immunotherapy Adoptive chemistry.chemical_compound Young Adult Tocilizumab Risk Factors Internal medicine Precursor B-Cell Lymphoblastic Leukemia-Lymphoma medicine Humans Prospective Studies Prospective cohort study Child Retrospective Studies Salvage Therapy business.industry Infant Retrospective cohort study Immunotherapy ORIGINAL REPORTS medicine.disease Prognosis Clinical trial Survival Rate Cytokine release syndrome chemistry Drug Resistance Neoplasm Child Preschool Monoclonal Female Neoplasm Recurrence Local business Cytokine Release Syndrome Follow-Up Studies |
| Zdroj: | J Clin Oncol |
| ISSN: | 1527-7755 |
| Popis: | PURPOSETo 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.METHODSChildren 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.RESULTSThe 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 ( P < .001), but persistence was not different ( P = .73). Event-free and overall survival were worse in the HTBC ( P = .004, P < .001, respectively). In the post hoc analysis, grade 4 CRS was observed in 27% versus 50% of patients in the PT and prior phase I cohorts, respectively ( P = .18).CONCLUSIONRisk-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. |
| Databáze: | OpenAIRE |
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