Outcomes of Patients Requiring ICU Admission after CD19 Directed CAR T-Cells

Introduction:Chimeric antigen receptor (CAR) T-cells are engineered T-cells that target specific antigens on tumor cell surfaces. CD19 directed CAR T-cells have demonstrated efficacy in B-cell lymphomas and B-cell acute lymphoblastic leukemia (B-ALL); however, patients are at risk for life-threatening complications including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Grade 3 ICANS and higher have been reported in 12-28% and Grade 3 CRS and higher in 1-23% in pivotal studies for B-cell lymphoma.¹ The majority, if not all, patients with Grade 3 ICANS and CRS require intensive care unit (ICU) admission. The long-term outcomes of patients requiring ICU admission after CD19 directed CAR T-cells are unknown.

Methods:Clinical data were retrospectively reviewed from consecutive patients with relapsed or refractory B-cell lymphomas and B-ALL treated with axicabtagene ciloleucel or tisagenlecleucel at a single institution from January 1, 2016 to July 1, 2020. Diagnosis of CRS and ICANS was based on the American Society for Transplantation and Cellular Therapy consensus grading.² Demographics, medical co-morbidities, therapeutic interventions, relapse rate, and all-cause mortality were assessed.

Results:Thirty-seven patients received CAR T-cells. Sixty-seven percent (n=25) of patients were male with a median age of 55 years (range 23 - 77). Eighty-nine percent of patients had large B cell lymphoma. Patients received a median of 3 prior therapies (range 1 - 6). The median IPI and ECOG scores at time of CAR T-cells administration were 3 and 1, respectively. Forty-three percent (n=16) of patients required ICU admission. The median length of ICU stay was 3.5 days (range 1 - 18). The median CRS and ICANS grades in patients requiring ICU admission were 2 and 3, compared to 2 and 0 in patients not requiring ICU admission, respectively. Thirty-one percent of ICU admitted patients had CRS grade 3 or above, and 61% had ICANS grade 3 or above. All 4 patients with B-ALL experienced grade 3 or above CRS and required ICU admission. Only 1 of the 37 patients (2.7%) patients died from CRS. Fifty-six percent of ICU patients experienced disease progression during follow-up, compared to 33% of non-ICU patients (OR 2.50, p = 0.20, 95% CI 0.55-12.11). Over a median follow up of 399 days, 56% of ICU patients died compared to 14% of non-ICU patients (OR 7.23, p = 0.01, 95% CI 1.32-54.27). The majority of deaths (58%) were due to disease progression.

Conclusions:A significant number of patients who receive CD-19 direct CAR T-cells require ICU admission. Patients requiring ICU admission after CAR T-cell have a worse outcome and overall survival, compared to non-ICU patients. The mortality rate of ICU admitted patients is primarily driven by death from disease.