Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.
Breyanzi® (lisocabtagene maraleucel) is an autologous chimeric antigen receptor (CAR) T-cell therapy that uses cells from a patient’s own immune system to target and fight cancer. This genetically modified autologous T-cell immunotherapy is directed at antigen CD19, and a single dose of Breyanzi contains 1:1 CAR-positive viable T cells of the CD8 and CD4 components, with each component supplied separately in 1 to 4 single-dose 5-mL vials. The dosage of Breyanzi is based on the number of CAR-positive viable T cells.1,2
Breyanzi is for autologous use only, as it is prepared from the patient’s own white blood cells, which are collected in a process referred to as leukapheresis. The time between receipt of the cells at the manufacturing facility and delivery to healthcare practitioners is typically 3 to 4 weeks, depending on conditions.4
Breyanzi is indicated for the treatment of adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), primary mediastinal LBCL, high-grade B-cell lymphoma, and follicular lymphoma grade 3B, who have:
- Disease refractory to first-line chemoimmunotherapy or relapse within 12 months after first-line chemoimmunotherapy
- Disease refractory to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplant (HSCT) because of comorbidities or age
- Relapsed or refractory disease after 2 or more lines of systemic therapy.2
Breyanzi is not to be given to patients with primary central nervous system lymphoma.3
Read more about DLBCL treatment
Pretreatment with a lymphodepleting chemotherapy regimen is given for 3 days to prepare the patient’s body for treatment with Breyanzi. This consists of cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day concurrently for 3 days. The Breyanzi infusion can then be administered 2 to 7 days after the lymphodepleting regimen is complete, either in an inpatient or outpatient setting. It must be administered in a Risk Evaluation and Mitigation Strategy (REMS)-certified healthcare facility, and patients must be monitored daily for a week and within proximity of the REMS facility for a month following infusion.2,4
FDA Approval History
Breyanzi received initial approval from the US Food and Drug Administration (FDA) on February 5, 2021, for the treatment of adults with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including DLBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. On June 24, 2022, the FDA approved the drug for 2 additional indications: (1) disease refractory to first-line chemoimmunotherapy or relapse within 12 months after first-line chemoimmunotherapy and (2) disease refractory to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy in patients not eligible for HSCT because of comorbidities or age. With the addition of the 2 new indications, more patients with relapsed or refractory LBCL are eligible for treatment with Breyanzi than with any other CAR T- cell therapy.5,6
Read more about DLBCL experimental therapies
Mechanism of Action
The generic name of Breyanzi, manufactured by Juno Therapeutics (a Bristol Myers Squibb company), is lisocabtagene maraleucel. It belongs to the class of drugs known as chimeric antigen receptor (CAR) T-cell therapies, which are autologous T-cell immunotherapies in which a patient’s own T cells are genetically modified to recognize and attack lymphoma cells. The drug binds to the CD19 protein, found on most lymphoma cells. Its composition is fixed to decrease variation in the number of CD8-positive and CD4-positive T cells in each dose.7,8
The CAR consists of an FMC63 monoclonal antibody-derived single-chain variable fragment (scFv), an immunoglobulin G4 hinge region, a CD28 transmembrane domain, a CD3 zeta activation domain, and a 4-1BB (CD137) costimulatory domain. The 4-1BB (CD137) signaling increases T-cell proliferation and Breyanzi persistence, whereas the CD3 zeta signaling is essential for initiating activation and anticancer action. The activation and multiplication of CAR T cells, the production of pro-inflammatory cytokines, and the cytotoxic death of target cells are all brought about by CAR binding to CD19 expressed on the surface of tumor and normal B cells.7,8
Efficacy in Trials and Trial Results
The FDA approval of Breyanzi was based on results from TRANSCEND NHL 001 (NCT02631044), an open-label, multicenter, single-arm trial conducted in adult patients with relapsed or refractory LBCL after at least 2 lines of therapy. To assess its efficacy, Breyanzi was administered to 192 patients in this study at single doses containing from 50 to 110 x 106 CAR-positive viable T cells. The overall response rate (ORR) was 73% (54% complete responses [CRs] and 19% partial responses [PRs]). The median duration of response (DOR) was 16.7 months in all responders. The median DOR was 1.4 months in the patients with a PR and was not reached in the patients with a CR. The treatment resulted in a best overall response of CR in 104 individuals. Of these, 65% experienced remission for at least 6 months, and 62% experienced remission for at least 9 months.2,7
Read more about DLBCL prognosis
The extended first-line indications for Breyanzi were based on the results from TRANSFORM (NCT03575351), a randomized, open-label, multicenter phase 3 trial. In this study, adults with LBCL both primary refractory or relapsed within 12 months after frontline therapy were randomized to receive either Breyanzi or standard therapy consisting of salvage immunochemotherapy and, if they responded, high-dose chemotherapy and HSCT. The results showed a well-established safety profile for Breyanzi, which more than quadrupled the median event-free survival (EFS) in comparison with standard therapy (10.1 vs 2.3 months). The drug outperformed the estimated 30-year standard of care significantly. Most of the patients treated with Breyanzi achieved a CR, whereas fewer than half who received standard therapy did so (66% vs 39%); the median duration of CR was not attained in the Breyanzi arm. Additionally, results demonstrated that Breyanzi significantly increased progression-free survival (PFS) in comparison with standard therapy (14.8 vs 5.7 months).5,7,9
The effectiveness of Breyanzi in the second-line setting was based on data from a multicenter phase 2 PILOT study (NCT03483103). This trial evaluated Breyanzi as a second-line therapy for adults with relapsed or refractory LBCL after frontline therapy who are not candidates for HSCT. With an ORR of 80%, the primary endpoint of the study, a CR rate of 54%, and a median CR duration of 1 month, Breyanzi demonstrated profound and long-lasting responses. The median DOR was 11.2 months, although in the patients with a CR, the median DOR was not attained.5
The most common nonlaboratory adverse reactions to Breyanzi, with an incidence of more than 30%, are fever, cytokine release syndrome (CRS), fatigue, musculoskeletal pain, and nausea. The most common grade 3 to 4 laboratory abnormalities, with an incidence of more than 30%, include decreases in lymphocytes, neutrophils, platelets, and hemoglobin. Breyanzi can also cause symptoms associated with neurologic toxicity, such as decreased consciousness, tremor, speech disorders, and seizures.2
Adverse effects of Breyanzi may also include headache, encephalopathy, infection, appetite loss, diarrhea, constipation, abdominal pain, vomiting, hypotension, tachycardia, dizziness, cough, and edema.7
Get full prescribing information for Breyanzi at MPR
Warnings and Precautions
Patients with a current infection or inflammatory disease should not receive Breyanzi. CRS in patients receiving Breyanzi may include life-threatening events. Tocilizumab can be used to treat severe or life-threatening CRS with or without corticosteroids. Patients on Breyanzi have also experienced neurologic toxicities, including fatal or life-threatening events, during or after the resolution of CRS and even without CRS. After Breyanzi treatment, the patient should be monitored for the development of any neurologic side effects. Breyanzi is accessible only through a REMS-certified healthcare facility because of the potential for CRS and neurotoxicity.1,9
Patients must be monitored during an infusion and closely examined for a week, to guard against hypersensitivity reactions and severe and fatal infections. Laboratory testing with complete blood cell counts is also required, as prolonged grade 3 or higher cytopenias have been noted following Breyanzi infusion. If signs or symptoms are found, treatment should be adjusted accordingly.2
Hypogammaglobulinemia may develop with this therapy, so that monitoring and consideration of the use of immunoglobulin replacement therapy are required. Secondary malignancies may also occur. In such cases, Bristol Myers Squibb should be contacted immediately.2
Patients should be advised not to drive or operate heavy machinery and not to engage in other potentially dangerous work for a minimum of 8 weeks following the administration of Breyanzi.2
- BREYANZI. RxList. Updated July 22, 2021. Accessed August 13, 2022.
- BREYANZI® (lisocabtagene maraleucel) suspension for intravenous infusion. Highlights of prescribing information. Juno Therapeutics. Revised June 2022. Accessed August 13, 2022.
- BREYANZI (lisocabtagene maraleucel). US Food and Drug Administration. Updated July 1, 2022. Accessed August 13, 2022.
- Stewart J. BREYANZI. Drugs.com. Updated July 6, 2022. Accessed August 13, 2022.
- U.S. FDA approves Bristol Myers Squibb’s CAR T cell therapy Breyanzi for relapsed or refractory large B-cell lymphoma after one prior therapy. News release. Drugs.com; June 24, 2022. Accessed August 13, 2022.
- FDA approves Breyanzi. News release. Drugs.com; February 5, 2021. Accessed August 13, 2022.
- Breyanzi (lisocabtagene maraleucel; liso-cel). wcg CenterWatch. Accessed August 13, 2022.
- Breyanzi. National Cancer Institute. Accessed August 13, 2022.
- BREYANZI – lisocabtagene maraleucel kit. National Library of Medicine, DailyMed. Updated June 1, 2022. Accessed August 13, 2022.
Reviewed by Debjyoti Talukdar, MD, on 8/29/2022.