Search

CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T cells are novel therapies showing great promise for patients with relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (B-NHL). Single-arm studies showed significant variations in outcomes across distinct CD19 CAR T-cell products. To estimate the independent impact of the CAR T-cell product type on outcomes, we retrospectively analyzed data from 129 patients with R/R aggressive B-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 1/2 clinical trial (NCT01865617). After adjustment for age, hematopoietic cell transplantation-specific comorbidity index, lactate dehydrogenase (LDH), largest lesion diameter, and absolute lymphocyte count (ALC), CAR T-cell product type remained associated with outcomes in multivariable models. JCAR014 was independently associated with lower cytokine release syndrome (CRS) severity compared with axicel (adjusted odds ratio [aOR], 0.19; 95% confidence interval [CI]; 0.08-0.46), with a trend toward lower CRS severity with tisacel compared with axicel (aOR, 0.47; 95% CI, 0.21-1.06; P = .07). Tisacel (aOR, 0.17; 95% CI, 0.06-0.48) and JCAR014 (aOR, 0.17; 95% CI, 0.06-0.47) were both associated with lower immune effector cell-associated neurotoxicity syndrome severity compared with axicel. Lower odds of complete response (CR) were predicted with tisacel and JCAR014 compared with axicel. 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 vs axicel became undetermined. Higher preleukapheresis LDH, largest lesion diameter, and lower ALC were independently associated with lower odds of CR. We conclude that CD19 CAR T-cell product type independently impacts toxicity and efficacy in R/R aggressive B-NHL patients.

Chimeric antigen receptor (CAR) T-cell therapy revolutionized treatment for many patients with aggressive relapsed or refractory large B-cell lymphoma (LBCL) Treatment can be complicated by clinically evident cytokine release syndrome (CRS), which is characterized by the development of fevers, hypoxia, and hypotension and can be life-threatening. Most patients treated with CAR T cells develop CRS, which is thought to represent an immune phenomenon. It was previously unknown if patients who do not develop CRS have reduced CAR T-cell activity and therefore are likely to have worse outcomes. We conducted a multicenter retrospective analysis that included 352 adult patients treated at eight academic medical centers within the United States who received axicabtagene ciloleucel or tisagenlecleucel for treatment of LBCL. Outcomes of interest included progression free survival, overall survival, complete response rate, and overall response rate. Of the included patients, 262 (74.4%) developed CRS. There was no significant difference in progression free (p=0.99) or overall survival (p=0.16) between patients who developed CRS and those who did not. Peak ferritin during treatment >5000 and lactate dehydrogenase greater than the institutional upper limit of normal prior to lymphodepleting chemotherapy were associated in multivariate analysis with significantly worse progression free and overall survival. There was no significant difference in complete response or overall response rate between patients who did and did not develop CRS. In this retrospective analysis, we report that patients who develop CRS have similar clinical outcomes compared to patients without CRS treated with commercial anti-CD19 CAR T cells.