Anti-BCMA CAR T cell compositions
The invention provides improved anti-BCMA CAR T cell compositions for adoptive T cell therapy for relapsed/refractory multiple myeloma.
1. A method of treating relapsed or refractory multiple myeloma (RRMM) in a human subject who has received at least 2 prior treatment regimens including a proteosome inhibitor and an immunomodulatory agent, comprising administering intravenously to the subject a single dose of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and anti-human B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) human T cells, wherein the dose is greater than 45.0×10 7 and less than 80.0×10 7 anti-BCMA CAR T cells, wherein the anti-BCMA CAR comprises amino acids 22-493 of the amino acid sequence of SEQ ID NO: 9, and wherein the dose is independent of bone marrow disease in the subject.
2. The method of claim 1 , wherein the subject has received at least 3 prior treatment regimens.
3. The method of claim 1 , wherein the subject was treated with daratumumab, lenalidomide, pomalidomide, bortezomib, and/or carfilzomib, prior to administration of the pharmaceutical composition.
4. The method of claim 1 , wherein the subject received an autologous hematopoietic stem cell transplant, prior to administration of the pharmaceutical composition.
5. The method of claim 1 , wherein the subject was lymphodepleted with cyclophosphamide 300 mg/m 2 and fludarabine 30 mg/m 2 prior to administration of the pharmaceutical composition.
6. The method of claim 1 wherein the dose is independent of body weight.
7. The method of claim 1 , wherein the anti-BCMA CAR is encoded by the nucleotide sequence set forth in SEQ ID NO: 10.
8. The method of claim 1 , wherein the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 9.
9. The method of claim 1 , wherein the anti-BCMA CAR T cells were produced by transduction with a lentiviral vector encoding the anti-BCMA CAR.
10. The method of claim 9 , wherein the lentiviral is a human immunodeficiency virus vector.
11. The method of claim 1 , wherein the T cells comprise CD8+ T cells.
12. A method of treating relapsed or refractory multiple myeloma (RRMM) in a human subject who has received at least 2 prior treatment regimens including a proteosome inhibitor and an immunomodulatory agent, comprising administering intravenously to the subject a single dose of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and anti-human B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) human T cells, wherein the dose is 45.0×10 7 ±20% anti-human BCMA CAR T cells, wherein the anti-BCMA CAR comprises amino acids 22-493 of the amino acid sequence of SEQ ID NO: 9, and wherein the dose is independent of bone marrow disease in the subject.
13. The method of claim 12 , wherein the subject has received at least 3 prior treatment regimens.
14. The method of claim 12 , wherein the subject was treated with daratumumab, lenalidomide, pomalidomide, bortezomib, and/or carfilzomib, prior to administration of the pharmaceutical composition.
15. The method of claim 12 , wherein the subject was lymphodepleted with cyclophosphamide 300 mg/m 2 and fludarabine 30 mg/m 2 prior to administration of the pharmaceutical composition.
16. The method of claim 12 , wherein the subject received an autologous hematopoietic stem cell transplant, prior to administration of the pharmaceutical composition.
17. The method of claim 12 , wherein the dose is independent of body weight.
18. The method of claim 12 , wherein the anti-BCMA CAR is encoded by the nucleotide sequence set forth in SEQ ID NO: 10.
19. The method of claim 12 , wherein the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 9.
20. The method of claim 12 , wherein the anti-BCMA CAR T cells were produced by transduction with a lentiviral vector encoding the anti-BCMA CAR.
21. The method of claim 20 , wherein the lentiviral is a human immunodeficiency virus vector.
22. The method of claim 12 , wherein the T cells comprise CD8+ T cells.