Jie Li1,2, Zhenyu Wu3,4, Naiqing Zhao5,6. 1. Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China. 2. Key Lab of Health Technology Assessment, Ministry of Health (Fudan University), Shanghai, China. 3. Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China. zyw@fudan.edu.cn. 4. Key Lab of Health Technology Assessment, Ministry of Health (Fudan University), Shanghai, China. zyw@fudan.edu.cn. 5. Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China. nqzhao1954@163.com. 6. Key Lab of Health Technology Assessment, Ministry of Health (Fudan University), Shanghai, China. nqzhao1954@163.com.
Abstract
INTRODUCTION: Chimeric antigen receptor T cells (CAR-T) with anti-CD19 have shown great promise in the treatment of relapsed and refractory non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL). Cytokine release syndrome (CRS) is the most significant and life-threatening side effect. This individual patient data (IPD) meta-analysis is to investigate the association of severe CRS with CAR-T dose and baseline factors. METHODS: We collected the individual patient-level data of 237 patients with NHL or ALL from 16 published papers. A logistic model was used to analyze the association of severe CRS incidence with CAR-T dose and baseline factors including age and baseline tumor burden. A generalized additive model (GAM) with logit link function was used to estimate the nonlinear response for severe CRS incidence with CAR-T dose and baseline factors. RESULTS: Severe CRS incidence was positively associated with current proposed CAR-T treatment infusion dose at a range of 0.2 × 106-5.0 × 106 T cells per kg of body weight in patients less than or equal to 25 years old. For patients over 25 years old the association was not significant. Significant association between severe CRS incidence and baseline tumor burden was also shown in this study. CONCLUSIONS: Our results provide novel insights that association between CAR-T treatment dose and severe CRS incidence only exists in patients less than or equal to 25 years old. Severe CRS incidence is associated with baseline tumor burden which indicates that tumor burden needs to be controlled with induced chemotherapy before CAR-T treatment.
INTRODUCTION: Chimeric antigen receptor T cells (CAR-T) with anti-CD19 have shown great promise in the treatment of relapsed and refractory non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL). Cytokine release syndrome (CRS) is the most significant and life-threatening side effect. This individual patient data (IPD) meta-analysis is to investigate the association of severe CRS with CAR-T dose and baseline factors. METHODS: We collected the individual patient-level data of 237 patients with NHL or ALL from 16 published papers. A logistic model was used to analyze the association of severe CRS incidence with CAR-T dose and baseline factors including age and baseline tumor burden. A generalized additive model (GAM) with logit link function was used to estimate the nonlinear response for severe CRS incidence with CAR-T dose and baseline factors. RESULTS: Severe CRS incidence was positively associated with current proposed CAR-T treatment infusion dose at a range of 0.2 × 106-5.0 × 106 T cells per kg of body weight in patients less than or equal to 25 years old. For patients over 25 years old the association was not significant. Significant association between severe CRS incidence and baseline tumor burden was also shown in this study. CONCLUSIONS: Our results provide novel insights that association between CAR-T treatment dose and severe CRS incidence only exists in patients less than or equal to 25 years old. Severe CRS incidence is associated with baseline tumor burden which indicates that tumor burden needs to be controlled with induced chemotherapy before CAR-T treatment.
Entities:
Keywords:
Acute lymphoblastic leukemia; Chimeric antigen receptor T cell; Generalized additive model; Individual patient data meta-analysis