Axi-cel Produces Enduring Real-World Responses in R/R Follicular Lymphoma

Enduring responses and a manageable toxicity profile were reported with axicabtagene ciloleucel (Yescarta; axi-cel) among patients with relapsed/refractory follicular lymphoma, according to real-world findings presented in a poster session at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition.

Among 238 patients at a median follow-up of 24.1 months (95% CI, 23.7-24.2), researchers reported an objective response rate (ORR) of 96% (n = 229; 95% CI, 93-98), including a complete response (CR) in 91% of patients (n = 216) and partial responses in 5% (n = 13).

At two years, the duration of response (DOR) was 70% (95% CI, 63-77), and the duration of complete response (DOCR) was 66% (95% CI, 58-73). Two-year progression-free survival (PFS) was 64% (95% CI, 57-71), and two-year overall survival (OS) was 84% (95% CI, 78-89).

Moreover, researchers reported that univariate and multivariable analysis demonstrated that prior bendamustine exposure was associated with reduced CR rates, as well as shorter DOR and PFS. Additionally, the presence of moderate or severe pulmonary comorbidity was associated with shorter OS.

“In our real-world experience, axi-cel in relapsed or refractory follicular lymphoma showed durable responses and a manageable safety profile similar to that seen in ZUMA-5,” said Aung Tun, MD, of The University of Kansas Health System, in a poster abstract session presentation of the data.

These data showed outcomes broadly consistent with those observed in the phase 2 ZUMA-5 trial (NCT03105336), which supported the FDA's accelerated approval of axi-cel in March 2021 for adult patients with relapsed or refractory follicular lymphoma after 2 or more prior lines of systemic therapy.

Tun continued: “The use of bendamustine as a lymphodepleting therapy was associated with a reduced efficacy; however that sample size was quite small, only 14 [patients], and it is difficult to draw conclusions. The prior use of bendamustine for lymphoma therapy was associated with fewer durable responses; however, that data on the timing of bendamustine exposure was not available. It is difficult to know whether the inferior outcome was because of the recent bendamustine therapy.”

Study Background and Patient Characteristics

Although the regulatory agency approved axi-cel treatment for this patient population in 2021, the study investigators explain in their poster that long-term assessments of safety and effectiveness are important because real-world patients have broader demographics, disease characteristics, and comorbidities than those who enroll in clinical trials.

Data for this observational, real-world analysis was collected from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, including consenting adults in the U.S. with relapsed or refractory follicular lymphoma who received commercial axi-cel between March 2021 and October 2023.

Investigators aimed to learn more about the ORR and CR rates of patients, as well as the DOR, PFS, and OS outcomes. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), along with prolonged cytopenias, clinically significant infections, subsequent neoplasms, and nonrelapse mortality, were also outcomes of interest to the study investigators.

Patients’ median age at infusion was 61 years (IQR, 55-68), with 38% of patients aged at least 65 years old; 58% of patients were male. Regarding Karnofsky performance score (KPS), most patients (54%) had a score from 90 to 100, 35% had a KPS of 80, and 11% had a KPS of 70 or less.

Clinically significant comorbidities were present in 75% of patients, and included cardiac (15%), hepatic (6%), and moderate to severe pulmonary comorbidities (18%). Over half of patients (67%) were diagnosed with stage 3 or 4 disease. Additionally, patients had received a median of four prior lines of therapy (IQR, 3-6), including prior autologous hematopoietic cell transplantation (14%), bendamustine (74%), and bridging therapy (32%).

Safety of Axi-Cel

Grade 1/2 CRS was observed in 74% of patients (n = 176), with grade 3 or higher CRS occurring in 4% (n = 10). ICANS was reported at a grade 1/2 in 42% of patients (n = 99), while grade 3 or higher ICANS were reported in 18% (n = 42). Prolonged neutropenia and prolonged thrombocytopenia were reported at any grade in 10% and 8% of patients, respectively.

In multivariable analyses of safety outcomes, patients who were reported to be 65 years or older had an increased risk of any-grade ICANS (OR/HR, 2.31; 95% CI, 1.18-4.50). Prior exposure to bendamustine for was associated with a lower risk of any-grade CRS (OR/HR, 0.30; 95% CI, 0.12-0.75), as well as a lower risk of any-grade ICANS (OR/HR, 0.23; 95% CI, 0.11-0.50).

The median time from treatment infusion to onset of CRS and ICANS was 5 (range, 1-14) and 8 days (range, 1-34), respectively. The median duration of both adverse effects was 5 days, respectively (range, 1-24; range, 1-42).

Moreover, investigators reported that the cumulative incidence of clinically significant infections at 6 months was 29% (95% CI, 23-35) and the cumulative incidence of myelodysplastic syndrome and acute myeloid leukemia as subsequent neoplasms at 24 months was 4% (95% CI, 2-8).

Overall, 14% of patients died from follicular lymphoma (n = 10), organ failure (n = 7), and infection (n = 10).

“[There were] no additional associations between key demographic or clinical variables with safety [that] were observed,” the investigators wrote in the poster.

Reference

Tun AM, Frank MJ, Iqbal M, et al. Real-world effectiveness and safety outcomes by age, comorbidity, frailty, and treatments prior to infusion in relapsed or refractory (R/R) follicular lymphoma patients treated with axicabtagene ciloleucel.Blood. 2025; 146(suppl 1): 5356. https://doi.org/10.1182/blood-2025-5356