Liso-Cel Drives Durable Longer-Term Benefit in R/R Follicular Lymphoma

Updated data from the phase 2 TRANSCEND FL trial (NCT04245839) demonstrated that treatment with lisocabtagene maraleucel (liso-cel; Breyanzi) led to durable complete responses (CRs) in patients with relapsed/refractory follicular lymphoma treated with the CAR T-cell therapy in the third line or beyond.¹

Data presented at the 52nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) showed that at 3 years of follow-up, patients treated with liso-cel (n = 103) achieved an overall response rate (ORR) of 97% (95% CI, 92%-99%), including a CR rate of 94% (95% CI, 88%-98%). The median duration of response (DOR) was not reached (NR; 95% CI, 38.5-NR), and the 36-month DOR rate was 70% (95% CI, 60%-76%).

Notably, the median progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) were all NR. The 36-month PFS, TTNT, and OS rates were 68% (95% CI, 58%-76%), 75% (95% CI, 70%-80%), and 86% (95% CI, 78%-92%), respectively.

“These results position liso-cel as a key therapeutic option for third-line-and-later relapsed/refractory follicular lymphoma,” said presenting study author Alejandro Martín García-Sancho, MD, PhD. García-Sancho is a staff physician of the Hematology Department of the University Hospital of Salamanca in Spain.

In May 2024, the FDA granted accelerated approval to liso-cel for the treatment of adult patients with relapsed or refractory follicular lymphoma who have received 2 or more prior lines of systemic therapy.² This regulatory decision was backed by prior data from TRANSCEND FL.

How was the TRANSCEND FL trial designed?

The phase 2, open-label, multicenter, multi-cohort study enrolled patients at least 18 years of age with relapsed/refractory, grade 1, 2, or 3a follicular lymphoma or marginal zone lymphoma.³ Patients with follicular lymphoma needed to have received at least 1 prior line of systemic therapy that included an anti-CD20 agent and an alkylating agent; patients who received at least 2 prior lines of therapy were eligible if they also received an anti-CD20 agent and an alkylating agent during prior therapy. An ECOG performance status of 0 or 1, as well as adequate organ function, were required.

All enrolled patients underwent leukapheresis prior to receiving lymphodepleting chemotherapy with fludarabine at 30 mg/m² per day plus cyclophosphamide at 300 mg/m² per day for 3 days. Liso-cel was then administered at a target dose of 100 x 10⁶ CAR-positive T cells 2 to 7 days following the completion of lymphodepletion.

ORR served as the trial’s primary end point. Secondary end points included CR rate, DOR, PFS, OS, safety, quality of life, and pharmacokinetics.

Within the enrolled third-line-or-later follicular lymphoma population, 114 patients underwent leukapheresis.¹ Three patients did not receive liso-cel due to adverse effects (AEs; n = 1) or no longer meeting eligibility criteria (n = 2). Four patients received a non-conforming product and were not included in the liso-cel–treated population (n = 107). Four patients from the treated population were not included in the efficacy population due to a lack of evaluable baseline PET/no measurable disease (n = 2) and no repeat PET following bridging therapy (n = 2).

In the liso-cel–treated population, the median age was 62 years (range, 23-80). Fifty-three percent of patients met modified Groupe d'Etude des Lymphomes Folliculaires (mGELF) criteria at their most recent relapse, and 32% of patients had bulky disease. Patients received a median of 3 prior lines of therapy (range, 2-10); prior treatments included hematopoietic stem cell transplantation (31%), rituximab (Rituxan) and lenalidomide (Revlimid; 21%), and bendamustine (61%). Sixty-four percent of patients were double refractory to anti-CD20 and alkylating agents, and 55% of patients experienced disease progression within 24 months of initial treatment with chemoimmunotherapy (POD24). Bridging therapy was administered to 41% of patients.

What additional long-term data were reported with liso-cel in relapsed/refractory follicular lymphoma?

Across subgroups of patients with POD24, bulky disease, or double-refractory disease, ORRs surpassed 95%. In patients with POD24 (n = 57), the 36-month DOR rate was 60% (95% CI, 46%-72%) vs 82% (95% CI, 66%-90%) for those without POD24 (n = 46). Patients with bulky disease (n = 31) experienced a 36-month DOR rate of 63% (95% CI, 43%-77%) vs 73% (95% CI, 61%-82%) for those without bulky disease (n = 72). Patients with double-refractory disease (n = 67) achieved a 36-month DOR rate of 63% (95% CI, 50%-74%) vs 83% (95% CI, 66%-92%) for those without double-refractory status (n = 36).

The 36-month PFS rates were 58% (95% CI, 43%-70%) for patients with POD24 and 80% (95% CI, 65%-89%) for patients without POD24; 61% (95% CI, 41%-75%) for patients with bulky disease and 71% (95% CI, 58%-80%) for patients without bulky disease; and 60% (95% CI, 47%-71%) for patients with double-refractory disease and 83% (95% CI, 66%-92%) for patients without double-refractory status.

In patients who received prior bendamustine within 12 months of leukapheresis (n = 5), the 36-month DOR and PFS rates were both 20% (95% CI, 1%-58%). For those who received prior bendamustine 12 to 24 months before leukapheresis (n = 9), the 36-month DOR and PFS rates were both 67% (95% CI, 28%-88%). For those at least 24 months removed from prior bendamustine exposure before undergoing leukapheresis (n = 47), the 36-month DOR and PFS rates were 77% (95% CI, 61.5%-87%) and 74% (95% CI, 58%-84%), respectively. Notably, patients with no prior bendamustine exposure (n = 42) achieved a 36-month DOR rate of 69% (95% CI, 52%-81%) and a 36-month PFS rate of 67.5% (95% CI, 50%-80%).

“Efficacy was consistently high in patients with high-risk characteristics…Patients who received bendamustine [more] than 12 months before leukapheresis had similar outcomes to the overall population and to patients without prior bendamustine exposure,” García-Sancho said.

Regarding safety, no new safety signals were reported with additional follow-up. Any-grade cytokine release syndrome (CRS) occurred in 59% of patients; however, no grade 4 or 5 CRS was reported, and grade 3 CRS was reported in 1% of patients. Neurologic AEs occurred in any grade in 16% of patients, although 2% had grade 3 toxicities, and no grade 4/5 neurologic AEs were reported.

Grade 3 or higher infections occurred in 12% of patients overall, including 7% of patients during the treatment-emergent (TE) period (infusion to 90 days after CAR T-cell therapy) and 7% after the TE period. Secondary primary malignancies were reported in 10% of patients; these were nonhematologic (7%) and hematologic (4%) in nature.

At the day 90 visit, 21% of patients had grade 3 or higher cytopenia. By day 365, this resolved to grade 2 or lower in 95% of patients (n = 18 of 19).

Disclosures: García-Sancho reported receiving consultancy fees from AbbVie, AstraZeneca, BeOne Medicines, Bristol Myers Squibb, Genmab, Gilead/Kite, GlaxoSmithKline, Janssen, Lilly, MSD, Regeneron, Roche, and Sobi; honoraria from AbbVie, AstraZeneca, BeOne Medicines, Bristol Myers Squibb, Gilead/Kite, Ideogen, Incyte Corporation, Janssen, Kyowa Kirin, Lilly, Regeneron, Roche, Sobi, and Takeda; and institution grants for research from Gilead/Kite.

References

1. Dreyling M, Ahmed S, García-Sancho AM, et al. Three-year efficacy and longitudinal safety of lisocabtagene maraleucel in patients with third-line or later follicular lymphoma from TRANSCEND FL. Presented at: 52nd Annual Meeting of the EBMT; March 22-25, 2026; Madrid, Spain. Abstract OS02-02.
2. FDA grants accelerated approval to lisocabtagene maraleucel for follicular lymphoma. FDA. May 15, 2024. Accessed March 23, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma
3. A study to evaluate the efficacy and safety of JCAR017 in adult subjects with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (NHL) (TRANSCEND FL). ClinicalTrials.gov. Updated November 5, 2025. Accessed March 23, 2026. https://clinicaltrials.gov/study/NCT04245839