Axicabtagene ciloleucel versus tisagenlecleucel for relapsed or refractory large B-cell lymphoma: a systematic review and meta-analysis

Transplant Cell Ther. 2024 Jan 26:S2666-6367(24)00171-4. doi: 10.1016/j.jtct.2024.01.074. Online ahead of print.

ABSTRACT

BACKGROUND: Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-directed chimeric antigen receptor (CAR-) T-cell therapies approved for relapsed/refractory aggressive B cell lymphomas (LBCL). Significant cost and complex manufacturing underscore the importance of evidence-based counseling regarding outcomes of these treatments. We aimed to examine efficacy and safety of axi-cel versus tisa-cel in patients with relapsed/refractory aggressive LBCL.

METHODS: We performed a systematic literature search of comparative studies evaluating outcomes in relapsed/refractory aggressive LBCL after treatment with axi-cel or tisa-cel. We calculated odds ratios (OR) and 95% confidence intervals (CI) were calculated for response, progression-free survival, overall surviva, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hematotoxicity. Meta-analysis and meta-regression were used to generate summary statistics.

RESULTS: A total of 2372 participants were included in 8 studies. The drop-out rate between apheresis and infusion was 13%v for axi-cel vs 18% for tisa-cel, and the median time from apheresis to infusion was 32 days vs 45 days. Axi-cel showed higher odds for complete responses (OR, 1.65; P<0.001) and was associated with higher odds for progression-free survival at 1 year after infusion (OR 0.60; P<0.001). Overall survival appeared to be improved with axi-cel (P=0.08), showing an OR of 0.84 (95% CI, 0.68-1.02), whereas cumulative incidence of non-relapse mortality was 11.5% for axi-cel vs 3.7% for tisa-cel (P=0.002). Main predictors for survival were LDH, ECOG, and response to bridging, while axi-cel maintained superior efficacy even in elderly patients. In terms of safety, axi-cel was associated with significantly higher odds for any CRS (OR, 3.23; P<0.001), but not for CRS of grade ≥3 (P=0.92). Axi-cel was associated with significantly higher odds for occurrence of severe ICANS grade ≥3 (OR, 4.03; P<0.001). In terms of hematotoxicity, axi-cel was significantly associated with higher odds for severe neutropenia at 1 month after infusion (OR, 2.06; P=0.003). As a result, axi-cel was associated with significantly increased resource utilization, including prolonged hospital stay, more frequent intensive care admission, and use of agents such as tocilizumab for toxicity management.

CONCLUSIONS: We provide strong evidence for higher efficacy of axi-cel versus tisa-cel in relapsed/refractory aggressive LBCL. Higher toxicity and non-relapse mortality seen with axi-cel may not counterbalance overall results, and rather highlight the need for timely intervention and careful selection of patients, balancing resource utilization and clinical benefit.

PMID:38281590 | DOI:10.1016/j.jtct.2024.01.074