CAR T-Cell Products Influenced Toxicity, Efficacy in B-Cell NHL

Certain CD19 chimeric antigen receptor (CAR) T-cell products were associated with different levels of adverse events and efficacy in patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (NHL), according to a recent study.

The researchers analyzed data from 129 patients with relapsed or refractory aggressive B-cell NHL treated with cyclophosphamide and fludarabine lymphodepletion followed by either a commercially available CD19 CAR T-cell therapy (axicabtagene ciloleucel [axicel] or tisagenlecleucel [tisacel]), or the investigational product JCAR014 on a phase I/II clinical trial.

“Our analyses show a strong and independent impact of the CAR T-cell product type on toxicity severity and anti-tumor efficacy,” the researchers wrote.

A higher percentage of patients received bridging therapy after leukapheresis with axicel and tisacel compared with JCAR014 (P<.001).

After adjustment for age, hematopoietic cell transplantation comorbidity index, lactate dehydrogenase (LDH), largest lesion diameter, and absolute lymphocyte count (ALC), the CAR T-cell product was associated with outcomes. JCAR014 was independently associated with lower cytokine release syndrome (CRS) severity compared with axicel (adjusted odds ratio [aOR]=0.19) and with a trend toward lower CRS severity with tisacel compared with axicel (aOR=0.47; P=.07).

There was lower immune effector cell-associated neurotoxicity syndrome severity with tisacel (aOR=0.17) and JCAR014 (aOR=0.17) compared with axicel.

The best overall response rates after axicel, tisacel, and JCAR014 were 75%, 58%, and 57%, respectively; the rates of complete response were 55%, 32%, and 40%, respectively. Lower odds of complete response were predicted with tisacel and JCAR014 compared with axicel.

In all, higher preleukapheresis LDH, largest lesion diameter, and lower ALC were independently associated with a lower odds of complete response.

The researchers noted, “An important limitation of our study is that differences in response assessments may have influenced the observed response rates in our dataset. Specifically, CT-only assessments were performed more frequently in tisacel patients (39%), due to distinct insurance policies between institutions/states for PET imaging coverage, compared to axicel (9%) and JCAR014 (10%) patients.”

These results were also presented in part at the 2021 ASCO Annual Meeting and the 2021 EHA Annual Meeting.

Gauthier J, Gazeau N, Hirayama AV, et al. Impact of CD19 CAR T-cell product type on outcomes in relapsed or refractory aggressive B-NHL. Blood. 2022. doi:10.1182/blood.2021014497