A Phase 1/2, open-label, multicenter, single-arm trial

Breyanzi®: THE ONE to deliver deep and durable responses in 3L+ CLL or SLL1

Primary endpoints: ORR (including CR and PR) and DOR1

Select secondary endpoints: safety, uMRD, PFS, and OS2

Patients were allowed to receive bridging therapy.1

The study population consisted mainly of patients with difficult-to-treat disease, with 83% having high-risk features* and 51% having bulky disease.1†

Breyanzi demonstrated deep and durable complete responses, with 87.5% of CRs maintained at 18 months1

DOR by best overall response1,3

Graph of duration of response by best overall response for CLL/SLL patients who had failed at least 2 prior treatments, including a BTKi and BCL-2i, in TRANSCEND CLL 004 trial

Primary endpoint:1

  • 45% ORR (29/65)
    (95% CI: 32.3, 57.5)
  • 20% CR (13/65)
    (95% CI: 11.1, 31.8)
  • 25% PR (16/65)
    (95% CI: 14.8, 36.9)
  • 35.3-month mDOR for all responders (95% CI: 12.4, NR)1
  • mDOR was not reached for those achieving a CR1
  • View an exploratory analysis of mPFS by minimal residual disease status

*Defined as patients having at least 1 of the following features: del(17p), mutated TP53, unmutated IGHV, or at least 3 chromosomal aberrations (complex karyotype).1

†Defined as having at least 1 lymph node lesion with the longest diameter of ≥5 cm.2

3L, third-line; CI, confidence interval; CLL, chronic lymphocytic leukemia; CR, complete response; DOR, duration of response; IGHV, immunoglobulin heavy chain gene; IRC, Independent Review Committee; iwCLL, International Workshop on Chronic Lymphocytic Leukemia™; mDoCR, median duration of complete response; mDoPR, median duration of partial response; mDOR, median duration of response; mPFS, median progression-free survival; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; SLL, small lymphocytic lymphoma; TP53, tumor protein 53; uMRD, undetectable minimal residual disease.

Median PFS of 12 months was observed in TRANSCEND CLL 0043‡

Graph of median progression-free survival (PFS) rates of Breyanzi 3L+ CLL/SLL patients in the TRANSCEND CLL 004 clinical trial

Analysis limitations:

  • PFS data are not in the Prescribing Information and should be interpreted with caution
  • PFS was a secondary endpoint in TRANSCEND CLL 004 and was 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 is not known

mPFS was not reached in patients who achieved a CR3

Median OS of 33.6 months was observed in TRANSCEND CLL 0043§

Graph of overall survival (OS) rates of 3L+ CLL/SLL patients in the TRANSCEND CLL 004 clinical trial
  • mOS was not reached in patients who achieved a CR3
  • mOS was 33.6 months (95% CI: 19.9, NR)3

Analysis limitations:

  • OS data are not in the Prescribing Information and should be interpreted with caution
  • OS was a secondary endpoint in TRANSCEND CLL 004 and was 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 OS is not known

*Defined as patients having at least 1 of the following features: del(17p), mutated TP53, unmutated IGHV, or at least 3 chromosomal aberrations (complex karyotype).1

†Defined as having at least 1 lymph node lesion with the longest diameter of ≥5 cm.2

‡Median follow-up 20.8 months (95% CI: 17.6, 24.4).3

§Defined as the time from Breyanzi infusion to the date of death due to any cause.2

3L, third-line; CI, confidence interval; CLL, chronic lymphocytic leukemia; CR, complete response; DOR, duration of response; IGHV, immunoglobulin heavy chain gene; mOS, median overall survival; mPFS, median progression-free survival; N/R, nonresponder; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; SLL, small lymphocytic lymphoma; TP53, tumor protein 53; uMRD, undetectable minimal residual disease.

Breyanzi: THE ONE studied in a broad range of patients, including older patients with more aggressive disease and multiple comorbidities

Hypothetical Breyanzi 3L+ CLL/SLL patients

Screening1

Broad enrollment criteria:

  • Adult patients with R/R CLL or SLL
  • Had failed at least 2 prior lines of therapy, including a BTKi and a BCL-2i
  • ECOG PS 0-1
  • LVEF ≥40%
  • CrCl ≥30 mL/min
  • ALT ≤5x ULN

Enrollment and leukapheresis (N=113)

CAR T-cells manufacturing

Breyanzi manufacturing1

Bridging chemotherapy was permitted between leukapheresis and lymphodepleting chemotherapy

CAR T-cells infusion bag

Lymphodepletion1‡

FLU 30 mg/m2 and CY 300 mg/m2 × 3 days

Infusion

Breyanzi infusion1

2 to 11 days after FLU/CY, planned dose of 100 × 106 CAR+ T cells

  • Primary endpoints: ORR (including CR and PR) and DOR1
  • Select secondary endpoints: safety, uMRD, PFS, and OS2

Patient and disease characteristics (N=65)1§

Hypothetical Breyanzi 3L+ CLL/SLL patients

66

Median age

(range: 49-82)

5 Median number prior therapies

(range: 2-12)

ECOG PS 0-1 100%
High-risk features* 83%
del(17p) 43%
TP53 mutated 45%
Complex karyotype∥ 62%
Unmutated IGHV 45%
Bulky disease† 51%

Patients studied had a median of 5 prior lines of therapy, plus high rates
of high-risk cytogenetics and bulky disease1

*Defined as patients having at least 1 of the following features: del(17p), mutated TP53, unmutated IGHV, or at least 3 chromosomal aberrations (complex karyotype).1

†Defined as having at least 1 lymph node lesion with the longest diameter of ≥5 cm.2

‡Measurable disease reconfirmed prior to lymphodepletion.2

§The planned dose of Breyanzi was 100 × 106 CAR-positive viable T cells.1

∥Defined as having at least 3 chromosomal aberrations.4

3L, third-line; ALT, alanine aminotransferase; BCL-2i, B-cell lymphoma 2 inhibitor; BTKi, Bruton tyrosine kinase inhibitor; CAR, chimeric antigen receptor; CLL, chronic lymphocytic leukemia; CR, complete response; CrCl, creatinine clearance; CY, cyclophosphamide; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; FLU, fludarabine; IGHV, immunoglobulin heavy chain gene; LVEF, left ventricular ejection fraction; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; R/R, relapsed or refractory; SLL, small lymphocytic lymphoma; TP53, tumor protein 53; ULN, upper limit of normal; uMRD, undetectable minimal residual disease.

References

  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2025.
  2. Siddiqi T, Maloney DG, Kenderian SS, et al. Lisocabtagene maraleucel in chronic lymphocytic leukaemia and small lymphocytic lymphoma (TRANSCEND CLL 004): a multicentre, open-label, single-arm, phase 1-2 study. Lancet. 2023;402(10402):641-654. doi:10.1016/S0140-6736(23)01052-8
  3. Data on file. BMS-REF-LIS-0046. Princeton, NJ: Bristol-Myers Squibb Company; 2024.
  4. Mato AR, Roeker LE, Jacobs R, et al. Assessment of the efficacy of therapies following venetoclax discontinuation in CLL reveals BTK inhibition as an effective strategy. Clin Cancer Res. 2020;26(14):3589-3596. doi:10.1158/1078-0432.CCR-19-3815

Important Safety Information

Indication

BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

  • adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

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. Three of 89 (3%) safety evaluable patients with R/R CLL/SLL developed IEC-HS. Time to onset of IEC-HS ranged from 7 to 18 days. Two of the 3 patients developed IEC-HS in the setting of ongoing CRS and 1 in the setting of ongoing neurotoxicity. IEC-HS was fatal in 2 of 3 patients. One patient had fatal IEC-HS and one had ongoing IEC-HS at time of death. 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 reactions (incidence ≥30%) in CLL/SLL are cytokine release syndrome, encephalopathy, fatigue, musculoskeletal pain, nausea, edema, and diarrhea. The most common Grade 3-4 laboratory abnormalities include neutrophil count decrease, white blood cell decrease, hemoglobin decrease, platelet count decrease, and lymphocyte count decrease.

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

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2009-US-2500225

09/2025