CD19 CAR T-Cell Product Type Impact on Outcomes in Relapsed/Refractory Non-Hodgkin Lymphoma

Study findings suggest that CD19 chimeric antigen receptor (CAR) T-cell product type, among axicabtagene ciloleucel (axicel), tisagenlecleucel (tisacel), and JCAR014, independently impacts toxicity and efficacy in relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (NHL).

“CD19-targeted [CAR]-engineered T cells are novel therapies showing great promise for patients with relapsed or refractory aggressive B-cell [NHL],” wrote Jordan Gauthier, MD, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, and colleagues.

“Single-arm studies showed significant variations in outcomes across distinct CD19 CAR T-cell products,” they added.

In this study, axicel was independently associated with higher immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS) severity, as well as higher efficacy than investigational JCAR014. Dr Gauthier and colleagues noted that higher preleukapheresis lactate dehydrogenase (LDH), largest lesion diameter, and lower absolute lymphocyte count (ALC) were factors independently associated with a lower efficacy and lower odds of complete response.

The analysis included 129 patients with relapsed/refractory aggressive B-cell NHL treated with cyclophosphamide and fludarabine lymphodepletion followed by either a commercially available CD19 CAR T-cell therapy: axicel or tisacel or the investigational product JCAR014 on a phase 1-2 clinical trial.

After adjustment for age, hematopoietic cell transplantation-specific comorbidity index, LDH, largest lesion diameter, and ALC, CAR T-cell product type remained associated with outcomes in multivariable models. JCAR014 was independently associated with lower CRS severity compared with axicel (adjusted odds ratio [aOR], 0.19; 95% confidence interval [CI]; 0.08 to 0.46), with a trend toward lower CRS severity with tisacel compared with axicel (aOR, 0.47; 95% CI, 0.21 to 1.06; P = .07).

Tisacel (aOR, 0.17; 95% CI, 0.06 to 0.48) and JCAR014 (aOR, 0.17; 95% CI, 0.06 to 0.47) were both associated with lower immune effector cell-associated neurotoxicity syndrome severity compared with axicel. Lower odds of complete response were predicted with tisacel and JCAR014, compared with axicel. However Dr Gauthier and colleagues noted that “although sensitivity analyses using either positron emission tomography- or computed tomography-based response criteria also suggested higher efficacy of axicel over JCAR014, the impact of tisacel versus axicel became undetermined.”

“We conclude that CD19 CAR T-cell product type independently impacts toxicity and efficacy in [relapsed/refractory] aggressive B-NHL patients,” they concluded.

Source:

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;139(26):3722-3731. doi:10.1182/blood.2021014497