Continuous blood purification successfully treated a fatal cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T cell therapy: case report
Abstract : Cytokine release syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) after Chimeric antigen receptor (CAR) T cell treatment are common, and severe CRS (sCRS) could be life threatening. IL-6 receptor antibody and steroid are recommended for CRS, but no clear strategies exist for steroid-resistant sCRS. Thus, this study reported a case of resistance to tocilizumab and pulse therapy of methylprednisolone while suffering from grade 4 CRS and ICANS. After plasma exchange for two times and continuous renal replacement treatment combined with ruxolitinib, the patient survived with only renal injury, and achieved complete remission with negative minimal residual disease.
Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood, with B lineage accounting for 75%–85% of all cases(1). Owing to the development of chemotherapy, B-ALL cure rates exceed 90% in children, but the cure rate for children with relapsed and/or refractory (R/R) B-ALL remains low(2, 3). In 2017, the CD19-targeted CAR T-cell product tisagenlecleucel was approved by the FDA for children and young adults (aged < 25 years) in R/R B-ALL(4). With the development of CAR T-cell immunotherapy, the CR rate has reached almost 90% in R/R B-ALL(5, 6).
As a response to CAR T-cell, cytokine release syndrome (CRS) is an inflammatory syndrome that occurred in 50%–90% of patients after infusion, with fever, hypoxemia, hypotension requiring multiple vasopressors, multiple-organ failure (MOF), or even a life-threatening condition(7). The standardized grading evaluation and first-line therapies for CRS are well established(7, 8). Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) have been described in 30%–64% of patients(9), repetitive seizures or coma have been described in 10%–20% patients, and 1% of patients died from rapid cerebral edema(10). For fatal CRS and ICANS, patient transfer to intensive care unit, mechanical ventilation, multiple vasopressors, anti-IL-6 therapy, high-dose methylprednisolone are recommended(9, 11). However, for patients resistant to methylprednisolone and tocilizumab, no definite treatment is available in published guidelines. Herein, a pediatric case of grade 4 CRS and grade 4 ICANS after CAR T-cell infusion was reported. Through therapeutic plasma exchange (TPE) and continuous renal replacement therapy (CRRT), CRS was controlled, MOF was improved, and ultimately, the patient achieved complete remission (CR). To the authors’ knowledge, this study was the first to report the use of TPE combined with CRRT for tocilizumab-resistant CRS and ICANS.