Leukemias, lymphomas, and other hematologic cancers:
Indications for: BREYANZI
Treatment of adults 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 ≥2 lines of systemic therapy.
Limitations of Use:
Not for treating primary CNS lymphoma.
Relapsed or Refractory LBCL After 1 Line of Therapy
The approval was based on data from the randomized, open-label phase 3 TRANSFORM study (ClinicalTrials.gov Identifier: NCT03575351), which evaluated the efficacy and safety of Breyanzi in 184 adults with relapsed or refractory LBCL within 12 months of first-line chemoimmunotherapy. Patients were randomly assigned 1:1 to receive either a single infusion of Breyanzi or standard therapy consisting of 3 cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT.
The primary endpoint was event-free survival (EFS) as determined by an independent review committee. Key secondary endpoints included complete response (CR) rate and progression-free survival (PFS).
Results showed that patients in the Breyanzi treatment arm achieved the following improvements vs those in the standard therapy arm, respectively:
- EFS: 10.1 months vs 2.3 months (hazard ratio [HR], 0.34; 95% CI, 0.22-0.52; P <.0001).
- CR rate: 66% (95% CI, 56-76) vs 39% (95% CI, 29-50) (P <.0001); median duration of CR was not reached (NR) in the Breyanzi arm (95% CI, 7.9-NR).
- Median PFS: 14.8 months vs 5.7 months (HR, 0.41; 95% CI, 0.25-0.66; P =.0001).
The efficacy of Breyanzi in the second-line setting was also supported by data from the single-arm, open-label, phase 2 PILOT trial (ClinicalTrials.gov Identifier: NCT03483103), which included 61 transplant-ineligible patients with relapsed or refractory LBCL after 1 line of chemoimmunotherapy. Findings showed an overall response rate of 80% (primary endpoint); 54% of patients achieved CR while 26% had a partial response. The median time to CR was 1 month (range, 0.8-6.9 months) and the median duration of response was 11.2 months (95% CI, 5.1-NR).
Relapsed or Refractory LBCL After 2 or More Lines of Therapy
The approval was based on data from a pivotal phase 1 study (TRANSCEND; ClinicalTrials.gov Identifier: NCT02631044) that assessed the efficacy and safety of Breyanzi in patients with relapsed or refractory large B-cell non-Hodgkin lymphoma after at least 2 lines of therapy. The primary outcome measures included treatment-related adverse events, dose-limiting toxicities and objective response rate (ORR). Key secondary end points included complete response rate, duration of response (DoR), and progression-free survival (PFS).
Among 192 patients in the main efficacy population, the ORR was 73% (95% CI, 67-80), of which 54% of patients (95% CI, 47-61) had complete response (CR) and 19% (95% CI, 14-26) had partial response (PR). The median DoR was 16.7 months (95% CI, 5.3-NR) among all responders; the median DOR was not reached (95% CI, 16.7-NR) among responders who achieved a CR; and the median DoR was 1.4 months (95% CI, 1.1-2.2) among responders who achieved a best response of PR. Of the 104 patients who achieved CR, 65% had remission lasting at least 6 months and 62% had remission lasting at least 9 months.
For autologous and IV use only; confirm patient identity prior to infusion. Do not use a leukodepleting filter. Give lymphodepleting chemotherapy (cyclophosphamide 300mg/m2/day IV + fludarabine 30mg/m2/day IV) for 3 days. Premedicate with APAP and diphenhydramine or other H1-antihistamine approx. 30–60mins prior to Breyanzi infusion; avoid prophylactic corticosteroids. Infuse Breyanzi 2–7 days after lymphodepleting chemotherapy. Relapsed/refractory after 1 line of therapy: give a single dose of 90–110×106 CAR-positive viable T cells (consisting of 1:1 CD8 and CD4 components), with each component supplied separately. Relapsed/refractory after ≥2 lines of therapy: give a single dose of 50–110×106 CAR-positive viable T cells (consisting of 1:1 CD8 and CD4 components), with each component supplied separately. May need >1 vial per component to achieve target dose. For dose preparation/administration and management of severe adverse reactions: see full labeling.
Cytokine release syndrome. Neurologic toxicities.
Risk of cytokine release syndrome (CRS); do not give to patients with active infection and/or inflammatory disorders. Have tocilizumab and emergency equipment readily available. Monitor daily for at least 7 days at the healthcare facility following infusion for signs/symptoms of CRS and neurologic toxicities. Continue to monitor for CRS for 4 weeks after infusion; at 1st sign, institute treatment with supportive care, tocilizumab and/or corticosteroids as indicated (see full labeling). Monitor for neurologic toxicities for 4 weeks after infusion and treat promptly (see full labeling). Monitor for infection, febrile neutropenia; evaluate, manage and treat appropriately. Screen for HBV, HCV, and HIV prior to cell collection for manufacturing. Consider concurrent antiviral therapy to prevent HBV reactivation in those with prior history of HBV. Monitor CBCs (prior to and after initiation), immunoglobulin levels after treatment. Pregnancy: not recommended. Verify pregnancy status prior to initiation. Nursing mothers.
CD19-directed genetically modified autologous T cell immunotherapy.
Concomitant live virus vaccines: not recommended for ≥6 weeks prior to lymphodepleting chemotherapy, during Breyanzi treatment, and until immune recovery. May cause false (+) results in certain HIV nucleic acid tests.
Fatigue, fever, CRS, musculoskeletal pain, nausea, headache, encephalopathy, infections (pathogen unspecified), decreased appetite, diarrhea, hypotension, tachycardia, dizziness, cough, constipation, abdominal pain, vomiting, edema; hypersensitivity reactions, HBV reactivation, hypogammaglobulinemia, neurologic toxicities, prolonged cytopenias, secondary malignancies (monitor).
Available only through a restricted REMS Program. For more information visit www.BreyanziREMS.com or call (888) 423-5436.
Generic Drug Availability:
Single-dose vials (5mL)—1, 2×4