FDA approves Breyanzi — first CAR-T therapy for marginal zone lymphoma in the US

On December 4, 2025 , the Food and Drug Administration (FDA) approved Breyanzi (lisocabtagene maraleucel) as the first CAR-T therapy in the United States for adults with marginal zone lymphoma (MZL) who have failed or relapsed after at least two lines of treatment. The approval is based on clinical data showing high response rates and responses considered durable up to a median follow-up of 21.6 months.

The approved indication targets adult patients with refractory or relapsed MZL after two or more systemic therapy lines, or those who have relapsed after hematopoietic stem cell transplantation (HSCT). The studied population included patients with particularly hard-to-control disease: the FDA statement highlights that nearly half of the treated patients had disease progression within two years of diagnosis or presented with refractory disease, conditions associated with poorer prognosis.

This clinical definition explains why the therapy is proposed as a “last-line” option for patients who no longer respond to conventional treatments: the goal is to achieve meaningful responses when standard options are ineffective.

Practically, the treatment is personalized and structured. The process begins with leukapheresis , the collection of the patient’s T-cells; these cells are then modified in the laboratory to express a chimeric antigen receptor (CAR) targeting CD19. Before infusion, preparative chemotherapy is administered to reduce the recipient’s lymphocytes; the single Breyanzi infusion is given two to seven days after completing lymphodepleting chemotherapy. For this reason, the treatment requires facilities capable of managing both the collection and production phase and the immediate clinical follow-up.

Regarding outcomes, the study reported in the regulatory dossier provided clear figures: 77 patients underwent leukapheresis, and 66 of them received the planned infusion. Among infused patients, the overall response rate (ORR) was 95.5% , while the complete response (CR) — meaning no radiological evidence of disease — was 62.1% . The median follow-up was 21.6 months , a period during which responses were considered durable; these numbers explain why the FDA viewed the efficacy/safety balance favorably for this selected population.

Safety remains a crucial element: the most common adverse reactions reported include cytokine release syndrome (CRS) , diarrhea, fatigue, musculoskeletal pain, and headache. Managing events such as CRS requires established protocols and immediate supportive therapies; for this reason, the clinical implementation of Breyanzi presumes centers with experience in cellular therapies and guidelines for monitoring and treating complications.

Why this option can make a difference. For patients with MZL who become refractory or relapse after multiple treatments, therapeutic alternatives are limited, and survival tends to decrease. A therapy that produces high responses and a CR rate above 60% in the studied context represents a therapeutic choice that, while not risk-free, offers a tangible opportunity to control the disease when traditional options fail.

Finally, organizational and clinical aspects. Breyanzi’s approval comes with regulatory designations — Priority Review and Orphan Drug — reflecting the clinical urgency and rarity of the condition. Practical access will require dedicated care pathways: selecting eligible patients, planning leukapheresis, coordinating product manufacturing, and follow-up programs to manage short- and long-term adverse effects.

Key Details and Data Breyanzi — active ingredient lisocabtagene maraleucel — is an autologous CAR-T therapy developed by Juno Therapeutics (Bristol-Myers Squibb) . It was approved on December 4, 2025 for adults with MZL (Marginal Zone Lymphoma) who have failed or relapsed after at least two systemic therapy lines or relapsed after HSCT (hematopoietic stem cell transplantation).

Target population: patients with refractory or relapsed MZL , i.e., those whose disease no longer responds to standard therapies or progresses after multiple treatments. In this context, treatment options are limited; the primary goal is achieving clinically meaningful responses — tumor reduction or remission — while improving quality of life when possible.

Clinical numbers (as reported in the FDA release):

Leukapheresis performed : 77 patients. Patients infused : 66. Overall response rate (ORR) : 95.5%. Complete response (CR) : 62.1%. Median follow-up : 21.6 months. What these numbers mean. An ORR of 95.5% indicates that nearly all infused patients showed some measurable benefit; a CR of 62.1% means that more than half had no radiological evidence of disease at assessment. The median follow-up of 21.6 months provides an early signal of response durability, although longer observation is needed to determine long-term benefit.

Treatment characteristics and care pathways:

Personalized treatment : starting from the patient’s cells (autologous), collected via leukapheresis and modified in the lab to express the anti-CD19 CAR. Therapeutic sequence : leukapheresis → preparative lymphodepleting chemotherapy → infusion of modified cells (typically 2–7 days after depletion). Dosing/occurrences : generally a single infusion per patient in the described protocol. Logistics and timing : product manufacturing requires specialized facilities; immediate post-infusion management requires intensive monitoring in the first weeks. Safety and management of complications: the most common adverse reactions reported are cytokine release syndrome (CRS) , diarrhea, fatigue, musculoskeletal pain, and headache. CRS is the most clinically significant risk because it can evolve rapidly and require specific supportive therapies (ward monitoring, immunomodulatory drugs, hemodynamic support). For this reason, Breyanzi administration requires centers experienced in cellular therapies with established protocols for early recognition and management of complications.

Limitations and critical considerations:

Cohort size : the numbers (66 infused patients) are significant for a rare setting but do not equate to large randomized studies necessary to draw universal conclusions for every subgroup. Generalizability : results obtained in experimental or controlled settings may differ in routine clinical practice; patient selection and logistical timing influence outcomes. Observation duration : median follow-up of 21.6 months is encouraging, but long-term data are needed to assess disease-free survival and late safety. Epidemiological context: MZL accounts for approximately 7% of B-cell non-Hodgkin lymphomas; in the United States, approximately 7,460 new cases per year are estimated. This profile defines it as rare but clinically relevant: even an effective therapy for a fraction of these patients can have a significant public health impact.

Regulation and access: Breyanzi received Priority Review and Orphan Drug designation, regulatory measures highlighting therapeutic urgency and disease rarity. Clinical implementation will depend on structured access pathways, reimbursement arrangements, and the capacity of national centers to adopt cellular therapy programs with trained personnel.

Limitations of use: not indicated for primary central nervous system lymphoma (PCNSL) — a condition with different biology and management.

Summary interpretation (non-technical): Breyanzi introduces a targeted solution for patients with MZL who have exhausted alternatives. It is a complex intervention, not a traditional drug: combining biotechnology, logistics, clinical expertise, and careful risk management. Initial numbers are promising — high response rates and a substantial proportion of complete remissions — but the clinical community will await longer-term data and broader real-world observations before redefining the MZL treatment algorithm.

Glossary CAR-T : cellular therapy that genetically modifies a patient’s T-cells to recognize tumor antigens and destroy malignant cells. Leukapheresis : blood cell collection procedure used to obtain T-cells for manipulation. Marginal zone lymphoma (MZL) : indolent B-cell lymphoma subtype accounting for about 7% of B-cell non-Hodgkin lymphomas. Complete response (CR) : absence of radiological evidence of disease at assessment. Cytokine release syndrome (CRS) : systemic inflammatory response that may occur after cellular therapies, with variable severity.

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