Factors Associated with Survival and Severe Cytokine Release Syndrome of Patients with Relapsed/Refractory B-ALL Receiving CD19 CAR-T Cell Therapy

Background: Chimeric antigen receptor-modified T (CAR-T) cells against CD19 have achieved great therapeutic effect in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, factors associated with the duration of survival and the occurrence of severe cytokine release syndrome (CRS) after CD19 CAR-T cell therapy have not been fully defined.

Patients and Methods: We analyzed 24 patients with relapsed/refractory B-ALL who received CD19 CAR-T cell therapy in a phase Ⅰ/Ⅱ clinical trial (ClinicalTrials.gov, NCT02349698). Infused CAR-T cell characteristics, its expansion kinetics in vivo, patient characteristics and laboratory parameters were analyzed for their correlation with overall survival (OS), progression-free survival (PFS), and the incidence of severe CRS.

Results: Sixteen patients achieved complete remission (CR), among which 13 achieved minimal residual disease-negative CR. Patients achieved CR had significantly prolonged OS and PFS compared with those who did not. Multivariable cox regression showed that lower peak of CAR-T cell expansion and the occurrence of severe CRS were significantly associated with both inferior OS and inferior PFS, and higher proportion of effector memory T cells in the infused cells was only significantly associated with inferior PFS. Nineteen patients developed CRS, among which 6 developed severe CRS. Compared patients with mild CRS, patients with severe CRS experienced worse vital sign instability and pancytopenia, higher incidences of coagulation and organ dysfunctions, and higher concentrations of procalcitonin and cytokines. Multivariable logistic regression showed that higher pretreatment disease burden was independent predictor of severe CRS.

Conclusions: Clinical and biological factors correlated with survival and severe CRS of refractory/relapsed B-ALL patients receiving CD19 CAR-T cell therapy were identified. These data may be helpful for improving the efficacy of CAR-T cell therapy, facilitating the recognition and early intervention of severe CRS.