fferences in efficacy or safety were observed between the different age subgroups or in comparison to the young adults in the trial.
The safety and efficacy of KYMRIAH in pediatric patients with relapsed or refractory DLBCL has not been established.
8.5 Geriatric Use
The safety and effectiveness of KYMRIAH have not been established in geriatric patients with r/r B-cell ALL. Clinical studies of KYMRIAH did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
11 DESCRIPTION
KYMRIAH™ (tisagenlecleucel) is a CD19-directed genetically modified autologous T cell immunotherapy comprised of autologous T cells that are genetically modified using a lentiviral vector to encode an anti-CD19 chimeric antigen receptor (CAR). The CAR is comprised of a murine single-chain antibody fragment (scFv) specific for CD19, followed by a CD8 hinge and transmembrane region that is fused to the intracellular signaling domains for 4-1BB (CD137) and CD3 zeta.
KYMRIAH is prepared from the patient’s peripheral blood mononuclear cells, which are obtained via a standard leukapheresis procedure. The mononuclear cells are enriched for T cells, then transduced with the lentiviral vector containing the anti-CD19 CAR transgene, and activated with anti-CD3/CD28 antibody coated beads. The transduced T cells are expanded in cell culture, washed, and formulated into a suspension, which then is cryopreserved. The product must pass a sterility test before release for shipping as a frozen suspension in a patient-specific infusion bag(s). The product is thawed prior to administration [see Dosage and Administration (2.3), How Supplied/Storage and Handling (16)]. The thawed product is a colorless to slightly yellow suspension of cells.
In addition to T cells, other cell populations, including monocytes, NK cells, and B cells, may be present. The formulation contains 31.25% (v/v) of Plasma-Lyte A, 31.25% (v/v) of 5% Dextrose/0.45% sodium chloride, 10 % Dextran 40 (LMD)/5% Dextrose, 20% (v/v) of 25% Human Serum Albumin (HSA), and 7.5% (v/v) Cryoserv® dimethylsulfoxide (DMSO).
Pediatric and Young Adult r/r B-cell ALL: A single dose of KYMRIAH may contain up to 2.5 x 108 CAR-positive viable T cells provided in a patient-specific infusion bag. Based on the patient’s weight reported at the time of leukapheresis, one of two possible dose ranges will be prepared for the patient:
For patients 50 kg or less: 0.2 to 5.0 x 106 CAR-positive viable T cells per kg body weight
For patients above 50 kg: 0.1 to 2.5 x 108 CAR-positive viable T cells
Adult r/r DLBCL: A single dose of KYMRIAH may contain 0.6 to 6.0 x 108 CAR-positive viable T cells provided in one or more patient-specific infusion bag(s).
The actual number of CAR-positive T cells in the product is reported on the Certificate of Analysis (CoA) that is shipped with KYMRIAH. The volume of CAR-positive viable T cells in an infusion bag ranges from 10 mL to 50 mL.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
KYMRIAH is a CD19-directed genetically modified autologous T cell immunotherapy which involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing malignant and normal cells. The CAR is comprise
