Axi-Cel More Efficacious With Higher Toxicity Than Tisa-Cel in Diffuse Large B-Cell Lymphoma

Axicabtagene ciloleucel (axi-cel; Yescarta; Kite Pharma) appears to be more efficacious but with a higher toxicity profile than tisagenlecleucel (tisa-cel; Kymriah’ Novartia) in patients with diffuse large B-cell lymphoma (DLBCL).

These findings were presented at the European Hematology Association (EHA) 2022 Congress, June 9-12, held both virtually and in Vienna, Austria, by Emmanuel Bachy, MD, PhD, Hospices Civils de Lyon, France.

“Axi-cel and tisa-cel have both demonstrated impressive clinical activity in R/R DLBCL. In a previous propensity score matching (PSM) analysis (Bachy et al., ASH 2021) allowing for balanced comparison between axi-cel and tisa-cel outcomes, we reported on a prolonged progression-free survival (PFS) but a higher toxicity associated with axi-cel compared with tisa-cel. No overall survival (OS) difference was observed but the follow-up was short (6 months),” Bachy and colleagues wrote.

Bachy and colleagues analyzed data from 809 patients with R/R DLBCL, at least 2 prior lines of therapy, and prior chimeric antigen receptor (CAR) T-cell therapy with either tisa-cel or axi-cel from 25 French centers part of the DESCAR-T registry. Patients included in the study were treated between July 2018 and October 2021. Of these patients, 60 were not infused due to progression or death and 20 for other reasons, leaving 729 to proceed to lymphodepletion and CAR-T infusion.

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The investigators used PSM to create a balanced covariate distribution between patients treated with tisa-cel and axi-cel. Covariates included age, sex, LDH level, C reactive protein, time between last treatment and infusion, ECOG performance status, Ann Arbor stage, prior lines of treatment, bridging and response to bridging, prior stem cell transplant, and others.

In a matched population of 209 patients treated with tisa-cel and 209 patients treated with axi-cel, best overall response rate (ORR) was 66% with tisa-cel and 80% with axi-cel and best complete response (CR) rate was 42% with tisa-cel and 60% with axi-cel (P <.001 for both). One-year progression-free survival (PFS) rate was 33% for tisa-cel and 47% for axi-cel (hazard rate [HR], 1.65 [95% CI, 1.26-2.18]; P = .0003) after a median follow-up of 11.7 months (95% CI, 10.5-12.0). One-year OS was 49% with tisa-cel and 63% with axi-cel (HR, 1.58 [95% CI, 1.13-2.21; P = .0072). Inverse Probability Treatment Weighting confirmed these findings.

In terms of safety, patients treated with axi-cel were more likely to experience grade 1 or 2 cytokine release syndrome (CRS; P = .004) but were not significantly more likely to experience grade 3 or higher CRS (9% vs 5%; P =.130). Patients treated with axi-cel were more likely to experience all grades of immune effector cell-associated neurotoxicity syndrome (ICANS; 48% vs 22%), with 29 patients (14%) treated with axi-cel experiencing at least grade 3 ICANS compared to 6 patients (3%) treated with tisa-cel.

“In conclusion, our matched-comparison study supports a higher efficacy but also a higher toxicity of axi-cel compared with tisa-cel in third or more treatment line for R/R DLBCL,” Bachy and colleagues concluded.

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REFERENCE

Bachy E, Le Gouill S, Sesques P, et al. A matched comparison of tisagenlecleucel and axicabtageneciloleucel car t cells in relapsed or refractory diffuse large b-cell lymphoma: A real-life Lysa study from the French DESCAR-T registry. Presented at: EHA 2022 Congress, June 9-12, Vienna, Austria and virtually. Abstract #S260.