Axi-Cel Is Associated With Higher ORR, Increased CRS/ICANS vs Tisa-cel in Older Patients With R/R DLBCL

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Findings from a retrospective comparative analysis showed that axicabtagene ciloleucel (Yescarta; axi-cel) was associated with higher complete response (CR) rates and reduced disease relapse/progression vs tisagenlecleucel (tisa-cel; Kymriah) in patients at least 70 years of age with relapsed/refractory diffuse large B-cell lymphoma (DLBCL); however, data presented at the 51st Annual EBMT Meeting showed that axi-cel was also associated with higher rates of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS).

Findings demonstrated that at day 100 post-infusion, patients treated with axi-cel (n = 682) experienced a CR rate of 69% compared with 49% for those treated with tisa-cel (n = 382). The estimated 1-year progression-free survival (PFS) rates were 51% (95% CI, 47%-55%) for axi-cel vs 37% (95% CI, 31%-42%) for tisa-cel (P < .001). The 1-year overall survival (OS) rates were 63% (95% CI, 59%-67%) for axi-cel compared with 56% (95% CI, 50%-61%) for tisa-cel.

The analysis also showed that axi-cel was associated with a higher 1-year non-relapse mortality (NRM) rate at 10% (95% CI, 8%-13%) compared with 6% (95% CI, 35-8%) for tisa-cel. The cumulative incidence of any-grade CRS within 30 days of the infusion of CAR T-cell therapy were 79% (95% CI, 75%-82%) with axi-cel vs 62% (95% CI, 57%-68%) with tisa-cel. The cumulative incidence of any-grade ICANS was 48% (95% CI, 44%-53%) with axi-cel vs 21% (95% CI, 16%-26%) for tisa-cel.

“Prophylaxis and management of early complications [such as] CRS and ICANS after axi-el and tisa-cel have improved in recent years,” lead study author Vanderson Rocha, MD, of São Paulo University in Brazil, said in a presentation of the data. “Further studies are needed to decrease toxicities after CAR T-cell therapy.”

Retrospective Analysis Rationale and Design

Although axi-cel and tisa-cel are both CD19-directed CAR T-cell therapies, Rocha explained that the agents have different efficacy and safety profiled. Specifically, he explained that the lower 4-1BB domain found in tisa-cel can lead to slower expansion and higher persistence, and the use of CD28 in axi-cel could lead to faster expansion with increased toxicity.

This retrospective, multicenter analysis evaluated outcomes of patients 70 years of age or older with relapsed/refractory DLBCL who received tisa-cel or axi-cel; data were gathered from the as EBMT Registry for patients treated between 2019 and 2024. The study population included patients from 146 centers across 15 European countries. Individuals treated with lisocabtagene maraleucel (Breyanzi) were excluded from the analysis.

Cox proportional hazards models were utilized to assess the primary variables of interest, including patient age and CAR T-cell product administered. Analyses were conducted on the full patient cohort with adjustment for key confounders, such as year of infusion, disease status at infusion, ECOG performance status, and sex. To further assess the robustness of findings, propensity score matching and models incorporating center-specific effects—including center frailty—were applied.

Key outcomes included rates of adverse effects, with a focus on CRS and ICANS, as well as NRM, relapse/progression incidence, PFS, and OS.

Baseline Patient Characteristics

The retrospective analysis included 1064 patients at least 70 years of age with DLBCL who received either tisa-cel (n = 382) or axi-cel (n = 682). The median age at diagnosis was 71.5 years (interquartile range [IQR], 69.3-74.3) for tisa-cel vs 71.3 years (IQR, 69.3-73.7) for axi-cel (P = .300). The median age at infusion was 74.7 years (IQR, 71.9-76.7) for tisa-cel compared with 73.6 years (IQR, 71.7-75.8) for axi-cel (P = .017). A greater proportion of patients were 70 to 75 years of age (tisa-cel, 61%; axi-cel; 68%) compared with 75 to 80 years of age (31%; 29%) and over 80 years of age (8.4%; 3.4%).

Sex distribution was identical across both cohorts, with males comprising 62% of the populations. ECOG performance status was similarly distributed, with most patients having a score of 0 or 1. An ECOG performance status of 2 or higher was reported in 9.7% of patients in the tisa-cel arm vs 7.9% of patients in the axi-cel arm.

With respect to disease characteristics at infusion, a higher proportion of patients in the tisa-cel cohort had relapsed or progressive disease (61%) compared with the axi-cel group (52%; P = .039). CR rates were 11% for tisa-cel and 10% for axi-cel; partial responses were more frequent in the axi-cel group (28% vs 21%).

The proportion of patients who had undergone prior autologous stem cell transplant (ASCT) was similar between groups (tisa-cel, 13%, axi-cel, 12%; P = .7). In terms of prior lines of non-ASCT therapy, 42% of patients in the axi-cel group had received only 1 prior line compared with 31% of patients in the tisa-cel group. Conversely, a higher proportion of patients in the tisa-cel arm had received at least 4 prior lines of therapy (21% vs 15%).

The median interval from apheresis to infusion was significantly longer in the tisa-cel group at 49 days (IQR, 41-66) compared with 39 days (IQR, 34-48) in the axi-cel group (P < .001). The majority of patients in both arms received a cyclophosphamide and fludarabine-based lymphodepletion regimen (tisa-cel, 93.7%; axi-cel, 93.9%).

The multivariable analysis examined the effect of various factors on different clinical outcomes for patients treated with either CAR T-cell therapy. Notably, year of infusion and disease status were correlated with CRS. Age, year of infusion, disease status, and ECOG performance status were associated with ICANS. Disease status and ECOG performance status were linked with relapse/progression, OS, and PFS outcomes. ECOG performance status was the only factor associated with NRM.

Disclosures: Rocha reported receiving speaking and advisory board honorarium from Kite and Gilead.

Reference

Rocha V, Mooyaart JE, Ram R, et al. Comparison of outcomes after CAR-T cell therapy (tisagenlecleucel or axicabtagene ciloleucel) in patients aged >70 years with diffuse large B-cell lymphoma: CTIWP-EBMT. Presented at: 51st Annual EBMT Meeting; March 30-April 2, 2025; Florence, Italy. Abstract OS17-06.