Risk-Adapted Preemptive Tocilizumab to Prevent Severe Cytokine Release Syndrome After CTL019 for Pediatric B-Cell Acute Lymphoblastic Leukemia: A Prospective Clinical Trial

被引：140

作者：

Kadauke, Stephan ^{[1
]}

Myers, Regina M. ^{[2
,3
,4
]}

Li, Yimei ^{[5
]}

Aplenc, Richard ^{[2
,3
,4
]}

Baniewicz, Diane ^{[2
,3
]}

Barrett, David M. ^{[2
,3
,4
]}

Leahy, Allison Barz ^{[2
,3
,4
]}

Callahan, Colleen ^{[2
,3
]}

Dolan, Joseph G. ^{[2
,3
,4
]}

Fitzgerald, Julie C. ^{[6
,7
]}

Gladney, Whitney ^{[8
]}

Lacey, Simon F. ^{[9
,10
]}

Liu, Hongyan ^{[5
]}

Maude, Shannon L. ^{[2
,3
]}

McGuire, Regina ^{[2
,3
]}

Motley, Laura S. ^{[2
,3
]}

Teachey, David T. ^{[2
,3
]}

Wertheim, Gerald B.

Wray, Lisa ^{[2
,3
]}

Di Nofia, Amanda M. ^{[2
,3
]}

Grupp, Stephan A. ^{[2
,3
]}

机构：

[1] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[2] Childrens Hosp Philadelphia, Cellular Therapy & Transplant Sect, Philadelphia, PA 19104 USA

[3] Childrens Hosp Philadelphia, Canc Immunotherapy Program, Philadelphia, PA 19104 USA

[4] Univ Penn, Dept Pediat, Perelman Sch Med, Div Oncol, Philadelphia, PA 19104 USA

[5] Univ Penn, Dept Biostat Epidemiol & Informat, Perelman Sch Med, Philadelphia, PA 19104 USA

[6] Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA

[7] Univ Penn, Philadelphia, PA 19104 USA

[8] Univ Penn, Ctr Cellular Immunotherapies, Perelman Sch Med, Philadelphia, PA 19104 USA

[9] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[10] Univ Penn, Ctr Cellular Immunotherapies, Philadelphia, PA 19104 USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2021年 / 39卷 / 08期

关键词：

CAR-T-CELLS; THERAPY; CHILDREN;

D O I：

10.1200/JCO.20.02477

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 (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). 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. (C) 2021 by American Society of Clinical Oncology

引用

页码：920 / +

页数：12

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