Axicabtagene ciloleucel (axi-cel; Yescarta®) has a higher efficacy but also higher toxicity than tisagenlecleucel (tisa-cel; Kymriah®) for the third-line or greater treatment of relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), according to a real-world use study published in Nature Medicine.

In patients with DLBCL receiving axi-cel, the best overall response rate/complete response rate (ORR/CR) was 80%/60% compared to 66%/42% in patients who received tisa-cel (P <.001 for both) after 1:1 propensity score matching.

These real-world results are similar to the results obtained in the pivotal trials for both therapies, with 82%/58% ORR/CR for axi-cel in the ZUMA-1 trial (NCT02348216) and 66%/42% for tisa-cel in the JULIET trial (NCT02445248).

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The 1-year progression-free survival was 46.6% for axi-cel compared to 33.2% for tisa-cel (P =.0003). The overall survival (OS) was also higher for patients receiving axi-cel, with a 1-year OS of 63.5% compared to 48.8% with tisa-cel (P =.0072).

In regard to safety, grade 1-2 cytokine release syndrome occurred significantly more often in patients receiving axi-cel than in those given tisa-cel (80.9% vs 66.5%; P <.001).

Immune effector cell-associated neurotoxicity syndrome (ICANS) was also more frequent in patients administered axi-cel than in those receiving tisa-cel, with grade 1-2 ICANS occurring in 34.9% vs 19.1% of patients (P <.001) and grade ≥3 occurring in 13.9% vs 2.9% of patients (P <.001), respectively. 

Hematological toxicity was also more frequently observed in patients with more severe cytopenia, neutropenia, thrombocytopenia, and anemia.

“Our matched comparison study supports a higher efficacy and also a higher toxicity of axi-cel compared to tisa-cel in the third or more treatment line for R/R DLBCL,” the authors said.

“Our findings could help in refining the choice of [chimeric antigen receptor (CAR)] T product for a specific patient based on the tradeoff between safety and efficacy,” the authors continued.

During the study, 809 patients with R/R DLBCL from 23 French centers were added to the DESCAR-T registry study (NCT04328298), but only 418 were included in this study following propensity score matching. The study cohort included 209 patients who received tisa-cel and 209 who received axi-cel.

Reference

Bachy E, Le Gouill S, Di Blasi R, et al. A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma. Nat Med. Published online September 22, 2022. doi:10.1038/s41591-022-01969-y