Reduced CAR T expansion post infusion is associated with poor survival in patients with large B cell lymphoma after two or more therapies

CD19 directed chimeric antigen receptor (CAR) T-cell therapy is now standard of care for relapsed/refractory large B-cell non-Hodgkin lymphoma. Despite good overall response rates, many patients still experience disease progression and therefore it is important to predict those at risk of relapse following CAR T-cell therapy. We performed a prospective study using a flow cytometric assay at a single treatment centre to assess early CAR T-cell expansion in vivo 6 - 9 days after CAR-T cell infusion. Early CAR T-cell expansion was used in conjunction with additional clinical risk factors to identify those at higher risk of relapse or treatment failure. Forty-four patients treated with commercial CD19 directed CAR T-cell therapy were included in the study, with a median follow up of 306 days. CAR T-cell expansion of >30 cells/μl was associated with a lower risk of disease progression or death (HR 0.34, p=0.048), but did not correlate with the risk of death alone. Patients who had poor early CAR T-cell expansion (<30 cells/μl) in addition to high lactate dehydrogenase (LDH) had significantly lower median progression-free and overall survival. High LDH alone was not a statistically significant risk factor for death or disease progression and therefore the interaction between CAR T-cell expansion and this clinical risk factor may be important in predicting response. Mean CAR T-cell count was higher in patients with grade 2-4 cytokine release syndrome (54.9 cells/μl) compared to grades 0-1 (25.5 cells/μl, p = 0.01). The methodology of this assay is easily reproducible outside of a clinical trial, allowing for real-life implementation within clinical settings. This study suggests that early assessment of CAR T-cell expansion can assist in identifying patients with poor overall survival who may benefit from early intervention or more intensive monitoring.