Lower Tumor Burden Correlates to Better Response Rates Among Patients With ALL Receiving CAR-T Therapy

The complete remission (CR) rate was higher among relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) patients under CD19 chimeric antigen receptor (CAR) T-cell therapy with lower than with higher tumor burden (TB), according to a recently-reported study.

However, there was no statistically significant difference in either overall survival (OS) or event-free survival (EFS) associated with degree of TB, nor did CAR T-cell expansion peaks differ.

“Importantly, the time points of TB measurement did not significantly affect the OS and EFS profiles regardless of whether the TBs were measured before or after fludarabine-cyclophosphamide preconditional chemotherapy. … Patients with a low R/R B-ALL TB yield more net benefits from CAR-T treatment than those with a high TB in terms of safety and CR rate,” wrote lead author Minghao Li, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, and co-authors.

Any correlation between TB and therapeutic efficacy has not been systematically studied, even though TB is significantly related to the severity of cytokine release syndrome (CRS) caused by CAR T-cells.

The researchers divided 78 patients into 2 groups, high and low TB, using a 5% TB as the boundary. The patients were treated with CD19 CAR T-cells, which are T cells expressing a CAR composed of an anti-CD19 single-chain antibody fragment with IL-6-specific shRNA.

The low TB was composed on 33 patients with minimal residual disease (MRD; bone marrow blast ranging from 0.01% to less than 5%). The remaining 45 patients were in the high TB group (bone marrow blasts equaling or exceeding 5%).

Of the entire cohort, 29 patients achieved MRD-negative CR (37.18%), 36 achieved MRD-positive or MRD status-unknown CR (46.15%), and 13 patients had no response (16.67%). The overall CR rate reached 83.33%.

The differential B-ALL TBs significantly affected the CR rates of patients treated with CAR-T 19, with rates of 93.94% and 75.56% in the low and high TB groups, respectively (P = .0358). The severity of CRS was significantly correlated with the TB level (P  =.0080).

Source:
Li M, Xue SL, Tang X, et al. The differential effects of tumor burdens on predicting the net benefits of ssCART-19 cell treatment on r/r B-ALL patients. Sci Rep. 2022 Jan 10;12(1):378.