输注后 CAR-T 细胞扩增减少与接受两种或以上治疗后大 B 细胞淋巴瘤患者生存不良相关

CD19-directed chimeric antigen receptor T cell (CAR-T) 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 therapy.

We performed a prospective study using a flow cytometry assay at a single treatment center to assess early CAR T cell expansion in vivo 6 to 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 greater risk of relapse or treatment failure. Forty-four patients treated with commercial CD19-directed CAR-T therapy were included in the study, with a median follow-up of 306 days. CAR T cell expansion of >30 cells/ L was associated with a lower risk of disease progression or death (hazard ratio, 0. 34; P = . 048), but did not correlate with the risk of death alone.

Patients who had poor early CAR T cell expansion (<30 cells/ L) in addition to high lactate dehydrogenase (LDH) had significantly lower median progression-free survival and overall survival. High LDH level alone was not a statistically significant risk factor for death or disease progression, and thus the interaction between CAR T cell expansion and this clinical risk factor may be important in predicting response.

The mean CAR T cell count was higher in patients with grade 2 to 4 cytokine release syndrome (CRS) compared to those with grade 0 to 1 CRS (54. 9 cells/ L versus 25. 5 cells/ L; P = . 01). The methodology of this assay is easily reproducible outside of a clinical trial, allowing for real-life implementation in 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.