P1398: AXICABTAGENE CILOLEUCEL VERSUS TISAGENLECLEUCEL CAR-T CELLS IN RELAPSED OR REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA
2023-08-01

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: 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. Aims: Meta-analysis of comparative studies to synthesize efficacy and safety outcomes. Methods: We included patients with relapsed/refractory aggressive B cell lymphomas receiving either axi-cel or tisa-cel and applied standard methodology following established guidelines. Only studies directly comparing axi-cel and tisa-cel were included. The PubMed, Embase, Cochrane Library and Web of Science databases were searched for clinical studies. 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. Survival outcomes were evaluated at 1 year. Pooled odds ratios (ORs) for overall survival, progression-free survival, non-relapse mortality, relapse rate, cytokine release syndrome (CRS), and neurotoxicity (ICANS) were calculated. We pooled event rates using a random effects framework. Bayesian modelling was performed for longitudinal comparisons. Incidence of hematotoxicity was calculated in an inverted variance framework. Results: A total of 1440 patients who underwent CAR-T cell therapy with axi-cel (n=770, 53%) or tisa-cel (n=670, 47%) were included. Among the infused patients, the median age was 60 years for axi-cel recipients and 64 years for tisa-cel recipients (P<0.001). The median time from apheresis to infusion was 35 days for axi-cel recipients and 50 days for tisa-cel recipients (P<0.001). Most patients included in the studies would have been ineligible for ZUMA-1 and JULIET trials that led to approval of the products, being 68% of the axi-cel recipients and 60% of the tisa-cel recipients, respectively. In terms of safety, axi-cel was associated with significantly higher odds for CRS of any grade (P<0.001), with an OR of 2.38 (95% confidence interval, 1.83-3.08), occurring in 84% of patients versus 70% of patients receiving tisa-cel. No significant difference between the 2 groups was observed for CRS of grade ≥3 (P=0.39), with an OR of 0.84 (95% confidence interval, 0.57-1.24), occurring in 8% of axi-cel versus 9% of tisa-cel patients. With respect to neurotoxicity, axi-cel was significantly associated with ICANS of any grade (P<0.001), with an OR of 3.27 (95% confidence interval, 2.57-4.16), occurring in 45% versus 29%; and axi-cel was associated with significantly higher odds for severe ICANS grade ≥3 (P<0.001; Figure 1A), with an OR of 4.40 (95% confidence interval, 3.00-6.44), occurring in 23% versus 6% in the tisa-cel group. Hematological toxicity and infections were also significantly more frequent and more severe with axi-cel than with tisa-cel. Any grade cytopenia at 1 month after CAR T infusion was observed in 46% of patients versus 29%. In terms of efficacy, axi-cel showed higher odds for overall and complete responses (P<0.001, respectively). Correspondingly, axi-cel was associated with better progression-free survival at 1 year (P<0.001), with an OR of 0.62 (95% confidence interval, 0.49-0.78; Figure 1B). Overall survival appeared to be improved with axi-cel (P=0.07), with an OR of 0.77 (95% confidence interval, 0.58-1.02). Summary/Conclusion: In conclusion, although only a randomized study could allow for an undisputable comparison between the 2 CAR-T products, our study strongly suggests higher efficacy but also a higher toxicity of axi-cel versus tisa-cel in ≥3rd line of treatment for aggressive lymphomas. Keywords: CAR-T, Diffuse large cell lymphoma