INDICATIONS

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

• Adult patients with relapsed or refractory mantle cell lymphoma (MCL).
• Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

IMPORTANT SAFETY INFORMATION

CYTOKINE RELEASE SYNDROME (CRS)

CRS, including fatal or life-threatening reactions, occurred following treatment with TECARTUS. CRS occurred in 93% (157/168) of patients with MCL, including ≥ Grade 3 CRS in 12% of patients in Study 1. Among the patients with MCL who died after receiving TECARTUS, one patient had a fatal CRS event. The median time to onset of CRS was 4 days (range: 1 to 13 days). The median duration of CRS was 7 days (range: 1 to 50 days). CRS occurred in 92% (72/78) of patients with ALL, including ≥ Grade 3 CRS in 26% of patients. Three patients with ALL had ongoing CRS events at the time of death. The median time to onset of CRS was 5 days (range: 1 to 12 days) and the median duration of CRS was 8 days (range: 2 to 63 days) for patients with ALL.

Confirm that a minimum of two doses of tocilizumab are available for each patient prior to infusion of TECARTUS. Monitor patients daily for at least 7 days following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 2 weeks after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES

Neurologic toxicities including immune effector cell-associated neurotoxicity syndrome (ICANS) which may be severe, life-threatening or fatal, occurred following treatment with TECARTUS. Neurologic events occurred in 80% (135/168) of patients with MCL, including ≥ Grade 3 in 33% of patients in Study 1. The median time to onset for neurologic events was 6 days (range: 1 to 32 days). The median duration of neurological events was 19 days (range: 1 to 828 days). Neurologic events occurred in 87% (68/78) of patients with ALL, including ≥ Grade 3 in 35% of patients. The median time to onset for neurologic events was 7 days (range: 1 to 51 days) with a median duration of 15 days (range: 1 to 397 days) in patients with ALL. For patients with MCL 105 (63%) patients experienced CRS before the onset of neurological events. Six (4%) patients did not experience CRS with neurologic events and 25 patients (15%) developed neurological events after the resolution of CRS. Neurologic events resolved for 167 out of 203 (82%) patients treated with TECARTUS. Fourteen patients (eight patients with MCL and six patients with ALL) had ongoing neurologic events at the time of death. For patients with ALL, neurologic events occurred before, during, and after CRS in 4 (5%), 57 (73%), and 8 (10%) of patients; respectively. Three patients (4%) had neurologic events without CRS. The onset of neurologic events can be concurrent with CRS, following resolution of CRS or in the absence of CRS.

Monitor patients daily for at least 7 days following infusion for signs and symptoms of neurologic toxicity/ICANS. Monitor patients for signs or symptoms of neurologic toxicities for 2 weeks after infusion and treat promptly. Advise patients to avoid driving for at least 2 weeks following infusion.

HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS/MACROPHAGE ACTIVATION SYNDROME (HLH/MAS)

HLH/MAS, including life-threatening reactions, occurred following treatment with TECARTUS. HLH/MAS occurred in 4% (3/78) of patients with ALL. Two patients experienced Grade 3 events and 1 patient experienced a Grade 4 event. The median time to onset for HLH/MAS was 8 days (range: 6 to 9 days) with a median duration of 5 days (range: 2 to 8 days). All three patients with HLH/MAS had concurrent CRS symptoms and neurologic events after TECARTUS infusion. Treatment of HLH/MAS should be administered per institutional standards.

HYPERSENSITIVITY REACTIONS

Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO) or residual gentamicin in TECARTUS.

SERIOUS INFECTIONS

Severe or life-threatening infections occurred in patients after TECARTUS infusion. Infections (all grades) occurred in 63% (105/168) of patients with MCL and 44% (34/78) of patients with ALL. Grade 3 or higher infections, including bacterial, viral, and fungal infections, occurred in 33% of patients with MCL and 29% of patients with ALL. TECARTUS should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines.

Febrile neutropenia was observed in 4% of patients with MCL and 35% of patients with ALL after TECARTUS infusion and may be concurrent with CRS. The febrile neutropenia in 27 (35%) of patients with ALL includes events of “febrile neutropenia” (11 (14%)) plus the concurrent events of “fever” and “neutropenia” (16 (21%)). In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated.

In immunosuppressed patients, life-threatening and fatal opportunistic infections have been reported. The possibility of rare infectious etiologies (e.g., fungal and viral infections such as HHV-6 and progressive multifocal leukoencephalopathy) should be considered in patients with neurologic events and appropriate diagnostic evaluations should be performed.

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. Perform screening for HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) in accordance with clinical guidelines before collection of cells for manufacturing.

PROLONGED CYTOPENIAS

Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and TECARTUS infusion. In patients with MCL, Grade 3 or higher cytopenias not resolved by Day 30 following TECARTUS infusion occurred in 55% (92/168) of patients and included thrombocytopenia (32%), neutropenia (42%), and anemia (14%). In patients with ALL who were responders to TECARTUS treatment, Grade 3 or higher cytopenias not resolved by Day 30 following TECARTUS infusion occurred in 20% (7/35) of the patients and included neutropenia (12%) and thrombocytopenia (12%); Grade 3 or higher cytopenias not resolved by Day 60 following TECARTUS infusion occurred in 11% (4/35) of the patients and included neutropenia (9%) and thrombocytopenia (6%). Monitor blood counts after TECARTUS infusion.

HYPOGAMMAGLOBULINEMIA

B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with TECARTUS. Hypogammaglobulinemia was reported in 14% (23/168) of patients with MCL and 9% (7/78) of patients with ALL. Monitor immunoglobulin levels after treatment with TECARTUS and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement.

The safety of immunization with live viral vaccines during or following TECARTUS 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 treatment, and until immune recovery following treatment with TECARTUS.

SECONDARY MALIGNANCIES

Patients treated with TECARTUS 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. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusions, and may include fatal outcomes.

Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥ 20%) in:

• patients with MCL included CRS, fever, encephalopathy, hypotension, infection with pathogen unspecified, viral infections, fatigue, tachycardias, chills, hypoxia, tremor, cough, musculoskeletal pain, nausea, edema, headache, constipation, diarrhea, decreased appetite, dyspnea, rash, insomnia, pleural effusion, aphasia, and motor dysfunction.
• patients with ALL included fever, CRS, hypotension, encephalopathy, tachycardia, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting.

The most common (≥ 20%) Grade 3-4 laboratory abnormalities in:

• patients with MCL included leukopenia, neutropenia, lymphopenia, thrombocytopenia, anemia, hypophosphatemia, hyperglycemia, blood uric acid increased, alanine aminotransferase increased, hyponatremia, and hypocalcemia.
• patients with ALL included leukopenia, neutropenia, lymphopenia, thrombocytopenia, anemia, hypophosphatemia, alanine aminotransferase increased, aspartate aminotransferase increased, hyperglycemia, and hypocalcemia.

Please see full Prescribing Information, including BOXED WARNING and Medication Guide.