Patterns of Use, Outcomes, and Resource Utilization among Recipients of Commercial Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed/Refractory Aggressive B Cell Lymphomas

Abstract

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-directed chimeric antigen receptor (CAR) T cell therapies approved for the treatment of relapsed/refractory aggressive B cell lymphomas. We present a multicenter retrospective study among centers that prescribe either commercial product to evaluate usage patterns, safety and efficacy outcomes, and resource utilization. Data collection included all patients from 8 US centers who underwent apheresis between May 1, 2018, and July 31, 2019. Patient selection, toxicity management, and disease assessment followed institutional practices. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy consensus criteria, and tumor responses were assessed according to the Lugano 2014 classification scheme. A total of 260 patients underwent apheresis, including 168 (65%) for axi-cel and 92 (35%) for tisa-cel. Among the infused patients, the median age was 59 years for axi-cel recipients and 67 years for tisa-cel recipients (P < .001). The median time from apheresis to infusion was 28 days for axi-cel recipients and 45 days for tisa-cel recipients (P < .001). Sixty-one percent of the axi-cel recipients and 43% of the tisa-cel recipients would have been ineligible for the ZUMA-1 and JULIET trials, respectively. Grade ≥3 CRS occurred in 9% of axi-cel recipients and in 1% of tisa-cel recipients (P = .017), and grade ≥3 ICANS was seen in 38% of axi-cel recipients and 1% of tisa-cel recipients (P < .001). Inpatient cell therapy infusion was common (92% in axi-cel recipients, 37% in tisa-cel recipients). The day 90 overall response rate was 52% in the axi-cel group and 41% in the tisa-cel group (P = .113), with complete response in 44% and 35%, respectively (P = .319). Twelve-month progression-free survival (42% versus 32%; P = .206) and overall survival (62% versus 59%; P = .909) rates were comparable in the axi-cel and tisa-cel groups. Baseline characteristics differed between the 2 groups, although response rates and survival outcomes were comparable, albeit lower than those in the pivotal trials. Safety and resource utilization appear to be key differentiators between axi-cel and tisa-cel.

Keywords: Aggressive large B cell lymphoma; CAR T cell therapy outcomes; CAR T cell toxicity; Chimeric antigen receptor T cell therapy; Resource utilization.

Figure 1:

CONSORT flow diagram. CAR = chimeric antigen receptor; Axi-cel = axicabtagene ciloleucel; Tisa-cel = tisagenlecleucel; PD = progressive disease

Figure 2:

Outcomes of axi-cel and tisa-cel (A) Non-relapse mortality by product. (B) Duration of response in responders at 90-day evaluation. (C) Progression-free survival from cell therapy infusion by product. (D) Overall survival from cell therapy infusion by product.