Axi-Cel and Tisa-Cel Show Comparable Adjusted Efficacy in Relapsed or Refractory Follicular Lymphoma

Key Takeaways:

• Among patients with relapsed or refractory follicular lymphoma (R/R FL), those receiving axicabtagene ciloleucel (axi-cel) had a higher overall response rate (ORR) and complete response rate (CRR) compared to those receiving tisagenlecleucel (tisa-cel).
• The axi-cel cohort had more reports of adverse events (AEs) compared to the tisa-cel cohort, particularly for immune effector cell-associated neurotoxicity (ICANS).
• Efficacy and safety outcomes were similar between trial-eligible and trial-ineligible patients, illustrating the impact of chimeric antigen receptor (CAR) T-cell therapy among patients with R/R FL.

CAR T-cell therapy has become the standard treatment for patients with R/R FL. However, real-world efficacy and toxicity data are limited because clinical trial cohorts do not represent the full patient population, which consists of older adults with comorbidities.

Study Methods and Outcomes

In a multicenter, real-world study of patients with R/R FL who received CAR T-cell therapy between 2021 and 2024, researchers compared the efficacy and toxicity of axi-cel and tisa-cel. An inverse probability of treatment weighting (IPTW) analysis was conducted to adjust for confounding.

The outcomes of this study included the ORR, CRR, progression-free survival (PFS), overall survival (OS), and rates of AEs. Investigators also compared outcomes between trial-eligible and trial-ineligible patients.

Patient Characteristics

The study included 136 patients with R/R FL: 100 (74%) received axi-cel, and 36 (26%) received tisa-cel. Most patients (80%) had grade 1 to 2 FL whereas less than one-fourth (20%) had grade 3a FL.

The median age of the whole sample was 61 years, and 70% of patients were male. Patients who received tisa-cel were older than those who received axi-cel, median age of 68 years vs 60 years, respectively. Female patients were more likely to receive tisa-cel than axi-cel, 47% vs 24%, respectively.

Of the 37 trial-ineligible patients, 30 (29%) received axi-cel and 7 (19%) received tisa-cel.

Efficacy Outcomes

For the entire study population, the ORR was 92% and the CRR was 85%. Patients who received axi-cel had an ORR of 96% and a CRR of 88%, significantly higher than the ORR and CRR for patients who received tisa-cel, 80% and 71%, respectively.

The overall median PFS for the entire cohort was 30.5 months. Axi-cel was associated with a significantly longer PFS compared to tisa-cel, 30.5 months vs 11.9 months, respectively.

A median OS was not reached within the study population, with comparable rates between axi-cel and tisa-cel, not reached vs 23.6 months, respectively.

Efficacy outcomes were comparable between trial-eligible and trial-ineligible patients.

After IPTW analysis, differences in effectiveness between the cohorts decreased, with many end points no longer being statistically significant.

Safety Outcomes

Most patients (75%) experienced any-grade cytokine release syndrome (CRS), with 5% having grade 3 or higher. Rates of CRS incidence were comparable between axi-cel and tisa-cel.

Any-grade ICANS occurred in approximately one-third (35%) of patients, with 15% having grade 3 or higher. Patients receiving axi-cel had higher rates of ICANS compared to patients receiving tisa-cel, 42% vs 17%, respectively.

Seventeen patients contracted an infection 30 days after CAR T infusion, with similar rates between the axi-cel and tisa-cel cohorts.

Trial-ineligible patients had higher rates of CRS compared to trial-eligible patients, 14% vs 2%, respectively. Otherwise, safety outcomes were comparable between groups.

After IPTW analysis, the axi-cel cohort was associated with significantly higher toxicity, particularly for ICANS, compared to the tisa-cel cohort.

Implications for Managed Care

These findings provide evidence on the real-world outcomes of CAR T-cell therapy among patients with R/R FL.

In the unweighted analysis, axi-cel was associated with increased efficacy, but higher toxicity compared to tisa-cel. After IPTW analysis, both regimens achieved comparable clinical benefits, although axi-cel still demonstrated higher toxicity.

According to the authors, “Given the differences between real-world and clinical trial populations, these data provide important context to inform patient counseling and clinical decision-making.”

Reference

Sharp J, Strati P, Bhatta S, et al. Real-world outcomes and toxicities of CAR-T in relapsed/refractory follicular lymphoma: a multicenter cohort study. Blood Adv. 2026;10(11):3757-3768. doi:10.1182/bloodadvances.2025019115