FDA Approves Brexucabtagene Autoleucel for Patients With R/R Mantle Cell Lymphoma

Key Clinical Summary: 

• Based on robust results from the ZUMA-2 trial, the FDA approved brexucabtagene autoleucel for adult patients with relapsed/refractory mantle cell lymphoma. 
• The therapy demonstrated high overall and complete response rates with durable remissions across all cohorts, including both BTK inhibitor–exposed and –naïve patients.
• These findings establish brexucabtagene autoleucel as a transformative treatment option in mantle cell lymphoma, though careful toxicity management and broader access remain critical considerations.

Michael Wang, MD, MD Anderson Cancer Center, Houston, Texas, discusses the recent FDA approval of brexucabtagene autoleucel (Tecartus®; Kite) for adult patients with relapsed/refractory mantle cell lymphoma. 

This approval was based on results from the ZUMA-2 trial which evaluated brexucabtagene autoleucel among heavily pretreated patients, including those who are Bruton tyrosine kinase inhibitor-naïve.

Transcript:

I'm Michael Wang, a Puddin Clarke Endowed Professor in the department of lymphoma and myeloma at MD Anderson Cancer Center in Houston, Texas. Today, I would like to share the details of the full FDA approval for the CD19 CAR T-cell therapy brexucabtagene autoleucel. 

Mantle cell lymphoma is a relatively rare lymphoma, but if you count the global incidence, it is about 33,000 people every year. Nowadays, patients live a long time so there is a bigger population of patients alive with mantle cell lymphoma. We used to use chemotherapy and we found that chemotherapy could not cure the disease so we added targeted therapies. One of the targeted therapies is Bruton's tyrosine kinase (BTK) inhibitor. We have the first-generation ibrutinib, which has been withdrawn from the US market, then second-generation covalent BTK inhibitors such as acalabrutinib and zanubrutinib, and more recently, we have the reversible BTK inhibitor pirtobrutinib. 

After covalent BTK inhibitors, patients have become BTK inhibitor-resistant and their survival is less than 1 year, according to multiple datasets. That is why ZUMA-2 was designed to overcome BTK inhibitor resistance. In cohort 1, we infused 2 million CAR T-cells, about 70 patients were enrolled for toxicity and efficacy, and efficacy was analyzed in 60 patients. The overall response rate was 87%, and the complete remission rate was 62%. At the time of presentation, with about 9 months of follow-up, the median progression-free survival was not reached. Based on the cohort 1 data of 60 patients, the FDA granted an accelerated approval for CD19 CAR T-cell therapy in 2020.

The ZUMA-2 clinical trial had 3 cohorts, the second cohort was similar to cohort 1, but the only difference was that cohort 2 infused 4 times fewer CAR T-cells, 0.5 million instead of 2 million. Because cohort 1 and cohort 2 were similar in efficacy and toxicity, we selected the 2 million CAR T-cell dose from cohort 1 and cohort 2 enrolled 14 patients and was then stopped. Cohort 3 enrolled 86 patients who had never received any BTK inhibitors, which is a major difference compared with cohorts 1 and 2, where patients had prior BTK inhibitor exposure. In cohort 3, the overall response rate was 91%, and the complete remission rate was 79%. After a follow-up of 23 months, the median duration of response had not been reached.

Based on all of these datasets, the FDA granted full approval of brexucabtagene autoleucel for relapsed/refractory mantle cell lymphoma. This is a milestone action from the FDA and very good news for patients. 

Regarding toxicities from CAR T-cell therapy, in the updated dataset, the mantle cell lymphoma data were pooled across the 3 cohorts, totaling 168 patients. In the pooled analysis, cytokine release syndrome occurred in 93% of patients, but severe CRS, grade ≥3 was only 12%. The median time to onset was 4 days, and the median duration was 7 days. Neurologic toxic events occurred in 80% of patients, including  grade ≥3 events in 33% of patients. The median time to onset was 6 days, and the median duration was 19 days. Infections of any grade occurred in about 63% of patients, with severe infections in 33%. Serious adverse events occurred in 65% of patients. The most common serious adverse events, occurring in >2%, included cardiac arrhythmias, tachycardia, fever, cytokine release syndrome, and infections.

A lot of patients ask, “less than 50% of patients receive this therapy, why?” One reason is that CAR T-cell therapy is expensive, and not all insurance plans support it so I really think medicine is also a socioeconomic model, and healthcare policy has a lot to do with accessibility of CAR T-cell therapy. We look to leaders to improve policies and allow more access for patients who need CAR T-cell therapy. 

Sources: 

Gilead. US FDA grants full approval of Kite’s Tecartus® for adult patients with relapsed or refractory mantle cell lymphoma. Accessed April 2, 2026. https://www.gilead.com/company/company-statements/2026/us-fda-grants-full-approval-of-kite-tecartus-for-adult-patients-with-relapsed-or-refractory-mantle-cell-lymphoma

Van Meerten T, Kersten MJ, Lacoboni G, et al. Brexucabtagene autoleucel for BTKi-naive relapsed/refractory mantle cell lymphoma: Primary analysis of ZUMA-2 cohort 3. Blood. Published online: March 19, 2026. doi:10.1182/blood.2025029734