Phase 2 Analysis Shows Deep, Durable Responses with Liso-Cel Across MZL Subtypes

According to the primary analysis of the phase 2 TRANSCEND FL study (NCT04245839), a single infusion of lisocabtagene maraleucel (liso-cel) provides a profound clinical benefit in patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL).^1,2

The multicenter TRANSCEND FL study represents the largest clinical evaluation to date of CD19-directed chimeric antigen receptor (CAR) T-cell therapy focused on a high-risk patient population that had exhausted at least 2 previous lines of systemic therapy.

Notably, those treated with liso-cel achieved a 95% overall response rate (ORR), meeting its primary end point with high statistical significance (P <.0001). The therapy showed deep and durable responses across all MZL subtypes, including nodal, extranodal–mucosa-associated lymphoid tissue (MALT), and splenic MZL. Furthermore, the safety profile was manageable, with low rates of severe cytokine release syndrome (CRS) and neurological events, supporting liso-cel as a viable new treatment option for a population with historically poor outcomes.

“Historically, patients with MZL who have had 1 to 2 treatments in the past struggle with maintaining a long-term response with subsequent therapies. We expect diminishing returns with each treatment,” said Reem Karmali, MD, MS, associate professor of medicine in the Division of Hematology and Oncology at the Feinberg School of Medicine and a co-author of the study, in a news release from Northwestern University.² “This is a population that has been routinely marginalized and not well studied in the setting of a clinical trial; therefore, innovations and new treatments in this group have been slow to develop.”

The primary end point of the study was ORR as determined by an independent review committee using Lugano 2014 criteria. The study successfully rejected the null hypothesis (ORR ≤ 50%). The ORR was 95% with a median follow-up of 24.1 months.

Liso-cel demonstrated deep and durable responses that were consistent across various patient subgroups. Notably, the study included patients with splenic MZL, a subtype that had not been evaluated in previous CAR T-cell studies for MZL (such as ZUMA-5 [NCT03105336]).³ High survival rates were maintained at the 24-month mark, particularly among patients who achieved a complete response.

While all patients in the study experienced at least 1 treatment-related adverse event, the safety profile of liso-cel was characterized as manageable and consistent with previous studies in other B-cell malignancies.¹

Adverse Events of Special Interest

• CRS: Grade 3 events occurred in 3 patients (4%). No grade 4 or 5 events were reported.
• Neurological events: Grade 3 events occurred in 3 patients (4%). No grade 4 or 5 events were reported.
• Infections:
• Grade ≥3 infections: 16% (11 patients)
• Treatment-emergent period (90 days): 9% (6 patients)
• Posttreatment-emergent period: 10% (7 patients)

TRANSCEND FL Study Design

The MZL cohort of the TRANSCEND FL study was designed to evaluate the efficacy and safety of liso-cel in a global setting across 30 sites in the US, Canada, Europe, and Japan.

Patients received a single infusion of 100 × 10⁶ CAR+ T cells. Of the total patients, 77 were leukapheresed, 67 received liso-cel, and 66 were evaluable for efficacy. Within the MZL cohort, 32 patients had nodal MZL, 18 had splenic MZL, and 17 had extranodal-MALT MZL. The median number of previous systemic therapies was 3 (range, 2–4).

Clinical Background and Therapeutic Need

MZL is an indolent B-cell malignancy comprising approximately 7% of all mature non-Hodgkin lymphomas. While characterized by slow growth, the disease presents significant clinical challenges:

• Treatment limitations: While patients often respond to initial CD20 monoclonal antibody therapies, repeated relapses are common.
• High-risk indicators: Patients experiencing progression of disease within 24 months (POD24) of initial treatment face inferior outcomes, including a higher risk of disease transformation and shorter overall survival.
• Unmet need in later lines: For patients in their third line of therapy or beyond, there is a critical lack of treatments capable of providing deep and durable responses. Current options like lenalidomide (Revlimid) plus rituximab (Rituxan) or Bruton tyrosine kinase inhibitors exist, but high-risk subsets require more effective interventions.

Comparative Analysis: Liso-Cel vs Axi-Cel

Prior to the TRANSCEND FL study, evidence for CAR T-cell therapy in MZL was largely limited to the ZUMA-5 study evaluating axicabtagene ciloleucel (Yescarta; axi-cel). The TRANSCEND FL results provide several advancements over previous data. For example, the ZUMA-5 trial had a total of 31 patients vs 67 patients in the TRANSCEND FL study. The TRANSCEND FL study included patients with splenic subtype MZL in addition to nodal and extranodal MZL. Additionally, there were less grade ≥3 infections in the TRANSCEND FL study vs the ZUMA-5 study.

REFERENCES

1. Palomba ML, Schuster S, Karmali R, et al. Lisocabtagene maraleucel in patients with relapsed or refractory marginal zone lymphoma (TRANSCEND FL): primary analysis results from the global, multicohort, single-arm, phase 2 study. The Lancet.Volume 407, Issue 10532, 7–13 March 2026, Pages 963-975. doi: 10.1016/S0140-6736(25)02435-3

2.CAR T-cell therapy improves survival in relapsed or refractory lymphoma. News release. Northwestern Medicine. Published March 4, 2026. Accessed March 18, 2026. https://tinyurl.com/4zjvduzc

3.A study of axicabtagene ciloleucel in participants with relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5). ClinicalTrials.gov. Updated December 23, 2025. Accessed March 18, 2026. https://clinicaltrials.gov/study/NCT03105336