BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma after two or more lines of systemic therapy, 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.
Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.

This site is intended for US healthcare professionals only.

Breyanzi: A Smart Option for a Broad Range of Patients

Breyanzi®: a smart option for a broad range of patients

Eligibility criteria in the TRANSCEND trial

Response to prior therapy2†

Refractory: 61%

Relapsed: 39%

Clinical fitness1

The trial included both patients who had previous stem cell transplants and patients who did not undergo transplant due to ineligibility or other reasons. There was no prespecified threshold for blood counts; patients were eligible to enroll if they were assessed to have adequate bone marrow function to receive LDC.

Patients with a CrCl of <30 mL/min, ALT >5 × ULN, LVEF <40%, or primary CNS lymphoma were excluded; additional inclusion/exclusion criteria applied.

ECOG PS

Graphic showing a caretaker overseeing a patient in bed

0-1

Organ function

Graphic depicting organ function criteria

LVEF ≥40%
CrCl ≥30 mL/min
ALT ≤5 × ULN

Of 299 patients who underwent leukapheresis, 204 (68%) received Breyanzi at the intended dose range of 50 to 110 × 106 CAR-positive viable T cells. Forty-four patients were not treated (29 due to death, 6 due to disease complications, 2 manufacturing failures, 7 for other reasons); 26 received Breyanzi outside of the intended dose range; 25 patients received out-of-spec product.§ Twelve of 204 patients receiving Breyanzi were not evaluable due to absence of PET positive disease at study baseline or after bridging therapy.1

* One patient was not evaluable for safety due to insufficient follow-up at the April 2019 data cutoff.
The status was refractory if a patient achieved less than a CR after 1L therapy or less than a CR or PR after 2L+ therapy. Otherwise, the status was relapsed.
There were 4 patients (1.5%) with ECOG PS 2.
§ CAR-positive T cells that did not meet the specifications for Breyanzi (manufacturing failures).

Patient profiles

Jamie

Head shot of 63 year old female patient named Jamie Head shot of 63 year old female patient named Jamie
  • 63 years old, R/R de novo DLBCL
  • Two prior lines of systemic therapy
  • Retired bus driver for a small city, now runs a local tour company
  • Moved in with her daughter, son-in-law, and their twin boys after her initial diagnosis

Hypothetical patient.
** Low tumor burden <50 cm2 SPD per IRC prior to LDC.

Response to prior therapy1-3

First-line therapy

  • Chemoimmunotherapy, achieved a CR
  • Relapsed after 13 months

Second-line therapy

  • Three cycles of salvage chemotherapy, achieved a CR
  • Underwent high-dose chemotherapy and ASCT
  • Relapsed after 6 months with low tumor burden**

Additional risk factors2

  • Relapsed to multiple lines of therapy
  • Relapse after ASCT

* Hypothetical patient.
Low tumor burden <50 cm2 SPD per IRC prior to LDC.

Clinical fitness1,2

ECOG PS

Graphic showing a caretaker overseeing a patient in bed

0

LVEF

Graphic of heart with a pulse rate inside. A plus sign is at the bottom left of the heart and a minus sign on the bottom right

60%

CrCl

Graphic showing kidneys with a plus sign on the bottom left and minus sign on the bottom right

69 mL/min

ASCT, autologous stem cell transplant; CR, complete remission; CrCl, creatinine clearance; DLBCL, diffuse large B-cell lymphoma; ECOG PS, Eastern Cooperative Oncology Group performance status; IRC, independent review committee; LDC, lymphodepleting chemotherapy; LVEF, left ventricular ejection fraction; SPD, sum of products of perpendicular diameters.

Diana

Head shot of 50 year old female patient named Diana Head shot of 50 year old female patient named Diana
  • 50 years old, R/R de novo DLBCL
  • Two prior lines of systemic therapy
  • Owns a hair salon and lives in a large city with her spouse, a retired high school teacher, age 65
  • Has 1 adult daughter who works with her at the salon and a teenage son who still lives at home

Hypothetical patient.
** High tumor burden ≥50 cm2 SPD per IRC prior to LDC. Markers of high tumor burden are SPD ≥50 cm2 and/or LDH ≥500 U/L.

Response to prior therapy1-3

First-line therapy

  • Chemoimmunotherapy, nonresponsive

Second-line therapy

  • Transplant-eligible, intent to transplant
  • Underwent salvage chemotherapy
  • High tumor burden and failed to respond; did not proceed to ASCT

Additional risk factors2

  • Primary refractory
  • Never achieved a CR after first-line therapy
  • Aggressive disease
  • High tumor burden**

* Hypothetical patient.
High tumor burden ≥50 cm2 SPD per IRC prior to LDC. Markers of high tumor burden are SPD ≥50 cm2 and/or LDH ≥500 U/L.

Clinical fitness1,2

ECOG PS

Graphic showing a caretaker overseeing a patient in bed

1

LVEF

Graphic of heart with a pulse rate inside. A plus sign is at the bottom left of the heart and a minus sign on the bottom right

68%

CrCl

Graphic showing kidneys with a plus sign on the bottom left and minus sign on the bottom right

92 mL/min

ASCT, autologous stem cell transplant; CR, complete remission; CrCl, creatinine clearance; DLBCL, diffuse large B-cell lymphoma; ECOG PS, Eastern Cooperative Oncology Group performance status; IRC, independent review committee; LDC, lymphodepleting chemotherapy; LDH, lactate dehydrogenase; LVEF, left ventricular ejection fraction; SPD, sum of products of perpendicular diameters.

Caleb

Head shot of 72 year old male patient named Caleb Head shot of 72 year old male patient named Caleb
  • 72 years old, R/R de novo DLBCL
  • Two prior lines of systemic therapy
  • Owner of an agricultural equipment dealership and repair shop
  • Lives with his spouse, age 60, on a small farm outside a medium-sized city; they have no children
  • A lifelong fly-fishing enthusiast, had to stop due to poor health, now sells handmade flies online

Hypothetical patient.
** Low tumor burden <50 cm2 SPD per IRC prior to LDC.

Response to prior therapy1-3

First-line therapy

  • Anthracycline-based
 chemoimmunotherapy
  • Achieved a CR, relapsed after 18 months

Second-line therapy

  • Transplant-eligible, intent to transplant
  • Underwent alternate salvage chemotherapy, achieved a CR
  • Did not proceed to ASCT due to reduced kidney function due to complications from salvage chemotherapy
  • Relapsed after 12 months with low tumor burden**

Additional risk factors2

  • Never undergone ASCT
  • Elderly with comorbidities
    • Reduced kidney function due to complication of salvage chemotherapy

* Hypothetical patient.
Low tumor burden <50 cm2 SPD per IRC prior to LDC.

Clinical fitness1

ECOG PS

Graphic showing a caretaker overseeing a patient in bed

1

LVEF

Graphic of heart with a pulse rate inside. A plus sign is at the bottom left of the heart and a minus sign on the bottom right

58%

CrCl

Graphic showing kidneys with a plus sign on the bottom left and minus sign on the bottom right

39 mL/min

ASCT, autologous stem cell transplant; CR, complete remission; CrCl, creatinine clearance; DLBCL, diffuse large B-cell lymphoma; ECOG PS, Eastern Cooperative Oncology Group performance status; IRC, independent review committee; LDC, lymphodepleting chemotherapy; LVEF, left ventricular ejection fraction; SPD, sum of products of perpendicular diameters.

Brett

Head shot of 70 year old male patient named Brett Head shot of 70 year old male patient named Brett
  • 70 years old, R/R de novo DLBCL
  • Two prior lines of systemic therapy
  • Retired firefighter who moved to the suburbs with his spouse, a nurse, age 60, to be closer to their children’s families
  • Volunteers at his grandchildren’s school and coaches their little league baseball team

Hypothetical patient.
** High tumor burden ≥50 cm2 SPD per IRC prior to LDC. Markers of high tumor burden are SPD ≥50 cm2 and/or LDH ≥500 U/L.

Response to prior therapy1-3

First-line therapy

  • Chemoimmunotherapy, achieved a CR
  • Relapsed after 27 months

Second-line therapy

  • Transplant non-eligible due to organ dysfunction
  • Underwent salvage chemotherapy, had stable disease
  • Disease progression after 3 months with high tumor burden**

Additional risk factors1

  • Transplant non-eligible
  • Elderly with comorbidities
    • Reduced kidney function
  • Did not achieve CR or PR after second-line therapy
  • High tumor burden**

* Hypothetical patient.
High tumor burden ≥50 cm2 SPD per IRC prior to LDC. Markers of high tumor burden are SPD ≥50 cm2 and/or LDH ≥500 U/L.

Clinical fitness1

ECOG PS

Graphic showing a caretaker overseeing a patient in bed

1

LVEF

Graphic of heart with a pulse rate inside. A plus sign is at the bottom left of the heart and a minus sign on the bottom right

43%

CrCl

Graphic showing kidneys with a plus sign on the bottom left and minus sign on the bottom right

38 mL/min

ASCT, autologous stem cell transplant; CR, complete remission; CrCl, creatinine clearance; DLBCL, diffuse large B-cell lymphoma; ECOG PS, Eastern Cooperative Oncology Group performance status; IRC, independent review committee; LDC, lymphodepleting chemotherapy; LDH, lactate dehydrogenase; LVEF, left ventricular ejection fraction; PR, partial response; SPD, sum of products of perpendicular diameters.

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Important Safety Information

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

  • 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.
  • BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.

Important Safety Information

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

  • 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.
  • BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.

Cytokine Release Syndrome (CRS)

CRS, including fatal or life-threatening reactions, occurred following treatment with BREYANZI. CRS occurred in 46% (122/268) of patients receiving BREYANZI, including ≥ Grade 3 (Lee grading system) CRS in 4% (11/268) of patients. One patient had fatal CRS and 2 had ongoing CRS at time of death. The median time to onset was 5 days (range: 1 to 15 days). CRS resolved in 119 of 122 patients (98%) with a median duration of 5 days (range: 1 to 17 days). Median duration of CRS was 5 days (range 1 to 30 days) in all patients, including those who died or had CRS ongoing at time of death.

Among patients with CRS, the most common manifestations of CRS include fever (93%), hypotension (49%), tachycardia (39%), chills (28%), and hypoxia (21%). 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.

Sixty-one of 268 (23%) patients received tocilizumab and/or a corticosteroid for CRS after infusion of BREYANZI. Twenty-seven (10%) patients received tocilizumab only, 25 (9%) received tocilizumab and a corticosteroid, and 9 (3%) received corticosteroids only.

Neurologic Toxicities

Neurologic toxicities that were fatal or life-threatening, occurred following treatment with BREYANZI. CAR T cell-associated neurologic toxicities occurred in 35% (95/268) of patients receiving BREYANZI, including ≥ Grade 3 in 12% (31/268) of patients. Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death. The median time to onset of the first event was 8 days (range: 1 to 46 days). The onset of all neurologic events occurred within the first 8 weeks following BREYANZI infusion. Neurologic toxicities resolved in 81 of 95 patients (85%) with a median duration of 12 days (range: 1 to 87 days). Three of four patients with ongoing neurologic toxicity at data cutoff had tremor and one subject had encephalopathy. Median duration of neurologic toxicity was 15 days (range: 1 to 785 days) in all patients, including those with ongoing neurologic events at the time of death or at data cutoff.

Seventy-eight (78) of 95 (82%) patients with neurologic toxicity experienced CRS. Neurologic toxicity overlapped with CRS in 57 patients. The onset of neurologic toxicity was after onset of CRS in 30 patients, before CRS onset in 13 patients, same day as CRS onset in 7 patients, and same day as CRS resolution in 7 patients. Neurologic toxicity resolved in three patients before the onset of CRS. Eighteen patients experienced neurologic toxicity after resolution of CRS.

The most common neurologic toxicities included encephalopathy (24%), tremor (14%), aphasia (9%), delirium (7%), headache (7%), dizziness (6%), and ataxia (6%). Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, have occurred in patients treated with BREYANZI.

CRS and Neurologic Toxicities Monitoring

Monitor patients daily at a certified healthcare facility during the first week following infusion, for signs and symptoms of CRS and neurologic toxicities. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 weeks after infusion; evaluate and treat promptly. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

BREYANZI REMS

Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:

  • Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
  • Certified healthcare facilities must have on-site, immediate access to tocilizumab.
  • Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS.
  • Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer BREYANZI are trained on the management of CRS and neurologic toxicities.

Further information is available at www.BreyanziREMS.com, or contact Bristol‐Myers Squibb at 1‐888‐423‐5436.

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. Infections (all grades) occurred in 45% (121/268) of patients. Grade 3 or higher infections occurred in 19% of patients. Grade 3 or higher infections with an unspecified pathogen occurred in 16% of patients, bacterial infections occurred in 5%, and viral and fungal infections occurred in 1.5% and 0.4% of patients, respectively. Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines.

Febrile neutropenia has been observed in 9% (24/268) of patients after BREYANZI infusion and 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.

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. Ten of the 11 patients in the TRANSCEND study with a prior history of HBV were treated with concurrent antiviral suppressive therapy to prevent HBV reactivation during and after treatment with BREYANZI. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

Prolonged Cytopenias

Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion. Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 31% (84/268) of patients, and included thrombocytopenia (26%), neutropenia (14%), and anemia (3%). Monitor complete blood counts prior to and after BREYANZI administration.

Hypogammaglobulinemia

B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with BREYANZI. The adverse event of hypogammaglobulinemia was reported as an adverse reaction in 14% (37/268) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 21% (56/268) of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 32% (85/268) 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. 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.

Effects on Ability to Drive and Use Machines

Due to the potential for neurologic events, including altered mental status or seizures, patients receiving BREYANZI are at risk for altered or decreased consciousness or impaired coordination in the 8 weeks following BREYANZI administration. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

Adverse Reactions

Serious adverse reactions occurred in 46% of patients. The most common nonlaboratory, serious adverse reactions (> 2%) were CRS, encephalopathy, sepsis, febrile neutropenia, aphasia, pneumonia, fever, hypotension, dizziness, and delirium. Fatal adverse reactions occurred in 4% of patients.

The most common nonlaboratory adverse reactions of any grade (≥ 20%) were fatigue, CRS, musculoskeletal pain, nausea, headache, encephalopathy, infections (pathogen unspecified), decreased appetite, diarrhea, hypotension, tachycardia, dizziness, cough, constipation, abdominal pain, vomiting, and edema.

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

Indication

BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma after two or more lines of systemic therapy, 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.

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

References

  1. Breyanzi [prescribing information]. Bothell, WA; Juno Therapeutics, Inc., a Bristol Myers Squibb Company. 2021.
  2. Data on file. Juno Therapeutics, Inc., a Bristol Myers Squibb Company. 2021.
  3. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001 ): a multicentre seamless design study. Lancet. 2020;396(10254):839-852.