Axicabtagene ciloleucel

YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate.

YESCARTA, a CD19-directed genetically modified autologous T cell immunotherapy, binds to CD19-expressing cancer cells and normal B cells. Studies demonstrated that following anti-CD19 CAR T cell engagement with CD19-expressing target cells, the CD28 and CD3-zeta co-stimulatory domains activate downstream signaling cascades that lead to T cell activation, proliferation, acquisition of effector functions and secretion of inflammatory cytokines and chemokines. This sequence of events leads to killing of CD19-expressing cells.

For autologous use only. For intravenous use only. Do NOT use a leukodepleting filter. Administer a lymphodepleting regimen of cyclophosphamide and fludarabine before infusion of YESCARTA. Verify the patient's identity prior to infusion. Premedicate with acetaminophen and an H1-antihistamine. Confirm availability of tocilizumab prior to infusion. Dosing of YESCARTA is based on the number of chimeric antigen receptor (CAR)-positive viable T cells. The target YESCARTA dose is 2 × 10 6 CAR-positive viable T cells per kg body weight, with a maximum of 2 × 10 8 CAR-positive viable T cells.

None. None.

Boxed warning (cytokine release syndrome, neurologic toxicities and secondary hematological malignancies): Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving YESCARTA. Do not administer YESCARTA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids. Hypersensitivity Reactions: Monitor for hypersensitivity reactions during infusion. Serious Infections: Monitor patients for signs and symptoms of infection, treat appropriately. Prolonged Cytopenias: Patients may exhibit Grade 3 or higher cytopenias for several weeks following YESCARTA infusion. Monitor complete blood counts. Hypogammaglobulinemia: Monitor and provide replacement therapy.

The most common adverse reactions (incidence ≥ 30%), excluding laboratory abnormalities, in patients with non-Hodgkin lymphoma are CRS, fever, hypotension, encephalopathy, fatigue, tachycardia, headache, nausea, febrile neutropenia, diarrhea, musculoskeletal pain, infections with pathogen unspecified, chills and decreased appetite. The most common Grade 3-4 laboratory abnormalities (≥ 30%) are leukopenia, lymphopenia, neutropenia, anemia, thrombocytopenia, and hypophosphatemia.

YESCARTA is supplied in a liquid nitrogen dry shipper at ≤ -150°C. At the treatment center, store YESCARTA frozen at ≤ -120°C (in a mechanical freezer or in the vapor phase of liquid nitrogen) up to the labeled expiration date. YESCARTA may be transferred from vapor phase of liquid nitrogen to mechanical freezer storage at ≤ -120°C only once and cannot be transferred back. YESCARTA may be stored at the treatment center for a single time at -80°C (+/- 10°C), for up to 90 days, and not exceeding the labeled expiration date. Do not return YESCARTA to storage at ≤ -120°C after storage at - 80°C.