The model of cytokine release syndrome in CAR T-cell treatment for B-cell non-Hodgkin lymphoma

Jianshu Wei,Yang Liu,J Joseph Melenhorst,Chuan Tong,Aibin Liang,John E J Rasko,Chunmeng Wang,Weidong Han,Wenbin Qian,Yajing Zhang,Wei Wang,Guanghai Dai

doi:10.1038/s41392-020-00256-x

Abstract

Chimeric antigen receptor T (CAR T) cell therapy has demonstrated efficacy in the treatment of haematologic malignancies. However, the accompanying adverse events, the most common of which is cytokine release syndrome (CRS), substantially limit its wide application. Due to its unique physiological characteristics, CRS in CAR T-cell treatment for B-cell non-Hodgkin lymphoma (B-NHL) may exhibit some special features. Although existing guidelines had greatly promoted the recognition and management of CRS, many recommendations are not fully applicable to B-NHL. Therefore, it is imperative to identify responses that are specific to CRS observed following CAR T treatment for B-NHL. Based on underlying biological processes and known pathophysiological mechanisms, we tentatively propose a new model to illustrate the occurrence and evolution of CAR T-cell-therapy-related CRS in B-NHL. In this model, tumour burden and bone marrow suppression are considered determinants of CRS. Novel phenomena after CAR T-cell infusion (such as local inflammatory response) are further identified. The proposed model will help us better understand the basic biology of CRS and recognize and manage it more rationally.

Highlights

INTRODUCTION Chimeric antigen receptorT (CAR T) cell therapy has emerged as a promising therapeutic approach for haematological malignancies,[1–6] and overall response rates of 52–82% and durable remission could be achieved in patients with refractory or relapsed (R/R) B-cell malignancies.[5,7–9] two Chimeric antigen receptorT (CAR T)-cell products targeting CD19 have been approved for R/R B-cell acute lymphoblastic leukaemia (B-ALL) and B-cell non-Hodgkin lymphoma (B-NHL) by the U.S Food and Drug Administration.[10,11]In vivo, infused CAR T cells will recognize and eliminate tumour cells expressing the target antigen
Grade 2: (1) Hypotension responds to IV fluids or low-dose vasopressors
(3) Management of constitutional symptoms and organ toxicities according to standard guidelines

Summary

Introduction

INTRODUCTION Chimeric antigen receptorT (CAR T) cell therapy has emerged as a promising therapeutic approach for haematological malignancies,[1–6] and overall response rates of 52–82% and durable remission could be achieved in patients with refractory or relapsed (R/R) B-cell malignancies.[5,7–9] two CAR T-cell products targeting CD19 have been approved for R/R B-cell acute lymphoblastic leukaemia (B-ALL) and B-cell non-Hodgkin lymphoma (B-NHL) by the U.S Food and Drug Administration.[10,11]In vivo, infused CAR T cells will recognize and eliminate tumour cells expressing the target antigen. The recognition and clinical management of CRS in CAR T-cell treatment for B-NHL Grade 2: (1) Hypotension responds to IV fluids or low-dose vasopressors. (2) Hypoxia requiring FiO2 < 40% (3) Grade 2 organ toxicity. Grade 3: (1) Hypotension needing high-dose or multiple vasopressor. (3) Grade 3 organ toxicity or grade 4 transaminitis.

Results

Conclusion