Bristol Myers Squibb’s Breyanzi Becomes First and Only CAR T Cell Therapy Approved by FDA for Relapsed or Refractory Marginal Zone Lymphoma
Breyanzi® CD19-directed chimeric antigen receptor (CAR) T cell therapy—for the treatment of adult patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have undergone at least two prior lines of systemic therapy. Developed by Bristol Myers Squibb (NYSE: BMY), this approval marks a pivotal moment in the management of a rare and often overlooked subtype of non-Hodgkin lymphoma, offering new hope to patients who have exhausted conventional treatment options.
A Transformative Milestone in Lymphoma Care
Marginal zone lymphoma (MZL) is an indolent (slow-growing) B-cell lymphoma that accounts for approximately 8–12% of all non-Hodgkin lymphoma cases. While many patients initially respond well to therapy, a significant subset experience disease recurrence, and some progress to a refractory state, where the cancer no longer responds to treatment. Managing these relapsed or refractory cases has historically been challenging, with limited therapeutic alternatives and a pressing need for more durable, effective solutions.
With this latest approval, Breyanzi becomes the first—and only—CAR T cell therapy authorized for R/R MZL, reinforcing its position as the broadest CD19-directed CAR T therapy across B-cell malignancies. This is the fifth cancer indication for which Breyanzi has received FDA approval, following its prior approvals in large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and now MZL.
Lynelle B. Hoch, President of the Cell Therapy Organization at Bristol Myers Squibb, emphasized the significance of this milestone:
“The FDA approval of Breyanzi for relapsed or refractory marginal zone lymphoma further solidifies it as the leading CD19-directed CAR T cell therapy covering the broadest range of B-cell malignancies. This approval in a fifth cancer type reflects our bold vision to bring the transformational potential of cell therapy to more patients. Breyanzi is the first and only CAR T cell therapy approved for this patient population, demonstrating Bristol Myers Squibb’s deep commitment to expanding access and reaching as many patients as possible with this innovative, practice-changing treatment.”
Clinical Evidence: High Response Rates and Durable Remissions
The FDA’s decision is grounded in compelling data from the MZL cohort of the TRANSCEND FL trial, an open-label, multicenter, multi-cohort, single-arm Phase 2 study evaluating liso-cel in patients with indolent B-cell lymphomas, including follicular lymphoma and MZL.
In the primary efficacy analysis set of 66 patients with R/R MZL treated in the third-line or later setting, Breyanzi demonstrated unprecedented efficacy:
- Overall Response Rate (ORR): 95.5% (95% CI: 87.3–99.1)
- Complete Response (CR) Rate: 62.1% (95% CI: 49.3–73.8)
Responses were assessed per Lugano criteria by an Independent Review Committee (IRC) using CT imaging, ensuring objective and standardized evaluation.
Perhaps even more encouraging was the durability of response. The median duration of response (mDOR) had not been reached at the time of analysis (95% CI: 25.59 months to not reached), with 90.1% of responders still in remission at 24 months—a remarkable outcome in a population historically prone to repeated relapses.
Dr. M. Lia Palomba, a principal investigator in the TRANSCEND FL study and a lymphoma and cell therapy specialist at Memorial Sloan Kettering Cancer Center, underscored the clinical impact:
“Patients living with marginal zone lymphoma generally see success with initial therapy, but a subset ultimately experience multiple relapses over many years, creating a pressing need for new treatment options with durable outcomes. The FDA approval of liso-cel in R/R MZL is a significant advancement in redefining the treatment landscape and providing patients with an option that has demonstrated high rates of responses with an established safety profile.”
Safety Profile: Manageable and Consistent Across Indications
Breyanzi is administered as a single, one-time infusion, but the full treatment process involves several critical steps: leukapheresis (blood collection), CAR T cell manufacturing, potential bridging therapy, lymphodepleting chemotherapy, infusion, and post-infusion monitoring for adverse events.
The safety profile observed in the MZL cohort aligned with that seen in previous trials across other B-cell malignancies. The most notable adverse events associated with CAR T therapy include Cytokine Release Syndrome (CRS) and neurologic toxicities, both of which carry FDA-mandated Boxed WARNINGS.
In the TRANSCEND FL MZL cohort:
- Any-grade CRS occurred in 76% of patients, with only 4.5% experiencing Grade ≥3 CRS—a severe but manageable complication.
- Common neurologic events included headache (21%), tremor (21%), encephalopathy (21%), dizziness (16%), and aphasia (10%). Grade ≥3 neurologic events were rare, with only 1.5% each for headache and encephalopathy.
Importantly, the manageable safety profile has enabled the possibility of outpatient administration for select, appropriate patients—expanding access and reducing the burden of prolonged hospitalization. This flexibility represents a meaningful advancement in the real-world delivery of CAR T therapy.
Broad Access and Comprehensive Support
Recognizing that access and support are as critical as the therapy itself, Bristol Myers Squibb has implemented robust infrastructure to support both patients and providers throughout the CAR T journey.
Breyanzi is broadly covered by commercial and government insurance programs in the U.S., helping to alleviate financial barriers. Additionally, the company offers Cell Therapy 360, a comprehensive digital platform that provides:
- Real-time updates on cell manufacturing status
- Educational resources for patients and caregivers
- Coordination support for treatment logistics
- Access to patient assistance programs
These services aim to streamline the complex CAR T therapy pathway—from referral to recovery—ensuring that patients can benefit from this innovation without being overwhelmed by logistical or administrative hurdles.
Redefining the Future of Lymphoma Treatment
The approval of Breyanzi for R/R MZL is more than a regulatory milestone—it signifies a paradigm shift in how indolent lymphomas are treated. Historically, MZL has been managed with watchful waiting, chemotherapy, immunotherapy, or targeted agents like BTK inhibitors. While these approaches offer benefit, they rarely lead to long-term remission in heavily pretreated patients.
CAR T cell therapy, by contrast, harnesses the power of the patient’s own immune system, genetically engineering T cells to recognize and destroy cancer cells expressing CD19—a protein commonly found on B-cell lymphomas. The high response rates and prolonged remissions seen with Breyanzi suggest it may not only control disease but potentially alter the natural history of R/R MZL.
This approval also reflects a broader trend in oncology: the expansion of cell therapy beyond aggressive lymphomas into indolent subtypes, where the goal is not just survival but sustained, treatment-free remission. As research continues, Breyanzi may eventually move into earlier lines of therapy, further improving outcomes for MZL patients.
With five FDA approvals across diverse B-cell malignancies, Breyanzi stands as a testament to the transformative potential of CAR T cell therapy and Bristol Myers Squibb’s leadership in the field. The company remains committed to ongoing research, including studies exploring combination therapies, earlier-line use, and novel CAR constructs to enhance efficacy and safety.
For patients with relapsed or refractory marginal zone lymphoma—once facing limited options and uncertain futures—the approval of Breyanzi offers not just a new treatment, but a new trajectory. In an era where precision medicine meets immune engineering, this milestone underscores a future where even the rarest cancers can be met with powerful, personalized solutions.
Source Link: https://www.bms.com/media.html
