A Phase 2, open-label, single-arm trial (N=61)

PILOT trial: First and only CAR T-cell therapy pivotal trial to exclusively enroll 2L LBCL patients who were transplant ineligible1,2

Primary endpoint: ORR1,2

Select secondary endpoints: CR rate, DOR, PFS, and OS1,2

Patients were required to meet ≥1 criteria that, per physician discretion, deemed them ineligible for transplant.1

Bridging therapy prior to receiving Breyanzi® was optional.1

Breyanzi: THE ONE to deliver deep and durable complete response in transplant-ineligible patients1

More than half of patients achieved complete response with Breyanzi1

Response rates in the PILOT trial (N=61)1-3*†

Graphic depicting response rates in Breyanzi PILOT trial

Median follow-up: 12.3 months (primary analysis); 18.2 months (final analysis)

Primary analysis1:

mDOR:
11.2 months (95% CI: 5.1, NR)

mDoCR:
NR (95% CI: 11.2, NR)

mDoPR:
2.1 months (95% CI: 1.4, 2.3)

Final analysis3:
Median DOR follow-up: 23 months (95% CI: 22.9, 23.3)

mDOR:
23 months (95% CI: 6.2, NR)

mDoCR:
NR (95% CI: 21.7, NR)

mDoPR:
2.1 months (95% CI: 1.4, 3.3)

*95% CIs in graph are for primary analysis. 95% CIs for final analysis: ORR: 68, 89; CR: 41, 67.3

†Per the Lugano criteria, as assessed by an IRC.1

‡2-sided 95% exact Clopper-Pearson confidence intervals.1

2L, second-line; CAR, chimeric antigen receptor; CI, confidence interval; CR, complete response; DOR, duration of response; IRC, Independent Review Committee; LBCL, large B-cell lymphoma; mDoCR, median duration of complete response; mDoPR, median duration of partial response; mDOR, median duration of response; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival.

Breyanzi: THE ONE with median overall survival not yet reached at final analysis3

Median PFS and OS for the Breyanzi PILOT trial at 24 months follow-up

Analysis limitations:

  • PFS and OS data are not in the Prescribing Information and should be interpreted with caution
  • PFS and OS were secondary endpoints in PILOT and were not statistically tested in the setting of a single-arm trial. It is not possible to determine if the observed effect is attributable to Breyanzi or to the natural history of the disease2
  • The statistical significance of PFS and OS are not known

*Reverse Kaplan-Meier method used to obtain median follow-up and its 95% CIs. Median follow-up (95% CI) for PFS, 24.0 months (23.8, 24.2); for OS, 24.3 months (24.0, 24.8).3

†Kaplan-Meier method used to obtain 2-sided 95% CIs.3

2L, second-line; CAR, chimeric antigen receptor; CI, confidence interval; CR, complete response; DOR, duration of response; LBCL, large B-cell lymphoma; mOS, median overall survival; mPFS, median progression-free survival; ORR, overall response rate; OS, overall survival; PFS, progression-free survival.

PILOT trial2

Trial design of Breyanzi PILOT clinical trial
  • Primary endpoint: ORR
  • Select secondary endpoints: CR rate, DOR, PFS, and OS

PILOT trial design and patient disposition1

Of 74 patients who underwent leukapheresis:

  • 61 (82%) received Breyanzi and comprise the main efficacy population
  • 1 (1.4%) received CAR-positive T cells that did not meet the product specifications for Breyanzi (manufacturing failure)
  • 12 (16%) did not receive CAR-positive T cells for other reasons

33% of patients were treated in an outpatient setting per physicians’ discretion1

Breyanzi: THE ONE studied in patients you are likely to see in your practice1,2

The PILOT trial included primary refractory and relapse patients

Characteristics (N=61)
Median age; range 74 years; 53-84 years
ECOG PS 0/1/2 at screening 31%/43%/26%
Primary refractory 53%
Relapsed 47%
LBCL subtypes  
DLBCL, NOS 51%
High-grade B-cell lymphoma 33%
DLBCL transformed from follicular lymphoma 15%

2L, second-line; CAR, chimeric antigen receptor; CR, complete response; CY, cyclophosphamide; DLBCL, diffuse large B-cell lymphoma; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; FLU, fludarabine; LBCL, large B-cell lymphoma; NOS, not otherwise specified; ORR, overall response rate; OS, overall survival; PET, positron emission tomography; PFS, progression-free survival.

References

  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2025.
  2. Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Lancet Oncol. 2022;23(8):1066-1077. doi:10.1016/S1470-2045(22)00339-4
  3. Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel for R/R LBCL in patients not intended for HSCT: final results of the phase 2 PILOT study. Blood Adv. Published online April 30, 2025. doi:10.1182/bloodadvances.2024015262

Important Safety Information

Indications

BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy 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), high-grade B cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:
  • refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
  • refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or
  • relapsed or refractory disease after two or more lines of systemic therapy.

Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.

Important Safety Information

WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, AND SECONDARY HEMATOLOGICAL MALIGNANCIES

  • Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving BREYANZI. Do not administer BREYANZI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids.
  • Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving BREYANZI, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with BREYANZI. Provide supportive care and/or corticosteroids as needed.
  • T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI.

Cytokine Release Syndrome

Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. In clinical trials of BREYANZI, which enrolled a total of 702 patients with non-Hodgkin lymphoma (NHL), CRS occurred in 54% of patients, including ≥ Grade 3 CRS in 3.2% of patients. The median time to onset was 5 days (range: 1 to 63 days). CRS resolved in 98% of patients with a median duration of 5 days (range: 1 to 37 days). One patient had fatal CRS and 5 patients had ongoing CRS at the time of death. The most common manifestations of CRS (≥10%) were fever, hypotension, tachycardia, chills, hypoxia, and headache.

Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI.

Neurologic Toxicities

Neurologic toxicities that were fatal or life-threatening, including immune effector cell-associated neurotoxicity syndrome (ICANS), occurred following treatment with BREYANZI. Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, also occurred.

In clinical trials of BREYANZI, CAR T cell-associated neurologic toxicities occurred in 31% of patients, including ≥ Grade 3 cases in 10% of patients. The median time to onset of neurotoxicity was 8 days (range: 1 to 63 days). Neurologic toxicities resolved in 88% of patients with a median duration of 7 days (range: 1 to 119 days). Of patients developing neurotoxicity, 82% also developed CRS.

The most common neurologic toxicities (≥5%) included encephalopathy, tremor, aphasia, headache, dizziness, and delirium.

CRS and Neurologic Toxicities Monitoring

Monitor patients daily for at least 7 days following BREYANZI infusion for signs and symptoms of CRS and neurologic toxicities and assess for other causes of neurological symptoms. Continue to monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 2 weeks after infusion and treat promptly. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. Manage neurologic toxicity with supportive care and/or corticosteroid as needed. Advise patients to avoid driving for at least 2 weeks following infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time.

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO).

Serious Infections

Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion. In clinical trials of BREYANZI, infections of any grade occurred in 34% of patients, with Grade 3 or higher infections occurring in 12% of all patients. Grade 3 or higher infections with an unspecified pathogen occurred in 7%, bacterial infections in 3.7%, viral infections in 2%, and fungal infections in 0.7% of patients. One patient who received 4 prior lines of therapy developed a fatal case of John Cunningham (JC) virus progressive multifocal leukoencephalopathy 4 months after treatment with BREYANZI. One patient who received 3 prior lines of therapy developed a fatal case of cryptococcal meningoencephalitis 35 days after treatment with BREYANZI.

Febrile neutropenia developed after BREYANZI infusion in 8% of patients. Febrile neutropenia may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated.

Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines. Avoid administration of BREYANZI in patients with clinically significant, active systemic infections.

Viral reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. In clinical trials of BREYANZI, 35 of 38 patients with a prior history of HBV were treated with concurrent antiviral suppressive therapy. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing. In patients with prior history of HBV, consider concurrent antiviral suppressive therapy to prevent HBV reactivation per standard guidelines.

Prolonged Cytopenias

Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion. In clinical trials of BREYANZI, Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 35% of patients, and included thrombocytopenia in 25%, neutropenia in 22%, and anemia in 6% of patients. Monitor complete blood counts prior to and after BREYANZI administration.

Hypogammaglobulinemia

B-cell aplasia and hypogammaglobulinemia can occur in patients receiving BREYANZI. In clinical trials of BREYANZI, hypogammaglobulinemia was reported as an adverse reaction in 10% of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 30% of patients. Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.

Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during BREYANZI treatment, and until immune recovery following treatment with BREYANZI.

Secondary Malignancies

Patients treated with BREYANZI may develop secondary malignancies. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol-Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing.

Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome (IEC-HS)

Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome (IEC-HS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. IEC-HS is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of IEC-HS should be administered per current practice guidelines.

Adverse Reactions

The most common adverse reaction(s) (incidence ≥30%) in:

  • LBCL are fever, cytokine release syndrome, fatigue, musculoskeletal pain, and nausea. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decrease, neutrophil count decrease, platelet count decrease, and hemoglobin decrease.

Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.

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2009-US-2500226

09/2025