Methods of administering chimeric antigen receptor immunotherapy
The disclosure provides cells comprising CD19-directed chimeric antigen receptor (CAR) genetically modified autologous T cell immunotherapy for the treatment of, e.g., 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. Some aspects of the disclosure relate to methods of treatment and monitoring following infusion of T cell therapy provided herein.
1 . A method for treating, high grade B-cell lymphoma in a patient comprising:
administering to the patient in need thereof an axicabtagene ciloleucel suspension by intravenous infusion at a dose between about 1×10 6 and about 2×10 6 CAR-positive viable T cells per kg body weight up to a maximum dose of about 2×10 8 CAR-positive viable T cells,
wherein axicabtagene ciloleucel is a CD19-directed genetically modified autologous T cell immunotherapy, comprising the patient's own T cells harvested and genetically modified ex vivo by retroviral transduction to express a chimeric antigen receptor (CAR) comprising an anti-CD19 single chain variable fragment (scFv) linked to CD28 and CD3-zeta co-stimulatory domains.
2 . The method of claim 1 , wherein the intravenous infusion is for a time period between 15 and 120 minutes.
3 . The method of claim 1 , wherein the intravenous infusion is for a time period up to 30 minutes.
4 . The method of claim 1 , wherein between 50 and 100 mL of the axicabtagene ciloleucel suspension is administered.
5 . The method of claim 1 , wherein about 68 mL of the axicabtagene ciloleucel suspension is administered.
6 . The method of claim 1 , wherein the axicabtagene ciloleucel suspension is infused from an infusion bag.
7 . The method of claim 6 , wherein the infusion bag is agitated during the infusion.
8 . The method of claim 1 , wherein the axicabtagene ciloleucel suspension is administered within 3 hours after thawing.
9 . The method of claim 1 , wherein the axicabtagene ciloleucel suspension further comprises albumin.
10 . The method of claim 9 , wherein albumin is present in an amount of about 2-3% (v/v).
11 . The method of claim 1 , wherein the axicabtagene ciloleucel suspension further comprises DMSO.
12 . The method of claim 1 , further comprising monitoring the patient for symptoms of cytokine release syndrome (CRS) daily for 7-10 days following the infusion, and administering to the patient a steroid:
(a) when CRS Grade 3 is observed; or
(b) when CRS Grade 2 is observed and treated but CRS symptoms do not improve after 24 hours.
13 . The method of claim 12 , wherein the monitoring is daily for 7 days following the infusion.
14 . The method of claim 12 , wherein the steroid is a corticosteroid.
15 . The method of claim 14 , wherein the corticosteroid is methylprednisolone or dexamethasone.