Method of use of anti-BCMA chimeric antigen receptors

Abstract

This invention provides a method for using anti-BCMA chimeric antigen receptors (CARs) to treat B-cell-related conditions such as cancers that express B-cell maturation antigens (BCMAs). [Solution] A method for treating a disease caused by B cell maturation material (BCMA) expressing cells, comprising: a. determining a first level of soluble BCMA (sBCMA) in a tissue sample derived from a subject; b. administering immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells) to the subject; and c. determining a second level of sBCMA in a tissue sample derived from the subject, wherein if the second level of sBCMA is higher than 30% of the first level of sBCMA, the subject is subsequently provided with non-CAR T cell therapy to treat the disease.

Claims

1. A method for treating diseases caused by B cell maturation agent (BCMA) expressing cells in subjects where such treatment is necessary, a. A step of determining a first level of soluble BCMA (sBCMA) in a tissue sample derived from the subject, b. The step of administering immune cells expressing a chimeric antigen receptor (CAR) against BCMA (BCMA CAR T cells) to the subject, and c. A step of determining the second level of sBCMA in a tissue sample derived from the subject. Includes, If the second level of sBCMA is higher than 30% of the first level of sBCMA, the subject is subsequently provided with non-CAR T-cell therapy to treat the disease. The method.

2. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. A step of determining a first level of soluble BCMA (sBCMA) in a tissue sample derived from the subject, b. A step of administering immune cells expressing a chimeric antigen receptor (CAR) against BCMA (BCMA CAR T cells) to the subject. c. A step of determining that the second level of sBCMA in the tissue sample derived from the subject is higher than 30% of the first level of sBCMA, and d. A step of providing non-CAR T-cell therapy to the subject based on the decision made in step c. The method, including the method.

3. The method according to claim 1, wherein if the second level of sBCMA is higher than 40% of the first level of sBCMA, the subject is provided with a non-CAR T-cell therapy for treating the disease.

4. The method according to any one of claims 1, 2, or 3, wherein the second level of sBCMA is determined 25 to 35 days after the administration step.

5. The method according to any one of claims 1, 2, or 3, wherein the second level of sBCMA is determined 28 to 31 days after the administration step.

6. The method according to any one of claims 1 to 5, wherein the subject is provided with non-CAR T cell therapy within 3 months, 2 months, or 1 month after the step of determining the second level of sBCMA.

7. A method for treating diseases caused by B-cell maturation material (BCMA) expressing cells, The process includes administering non-CAR T-cell therapy to patients diagnosed with the disease, The patient had previously received immune cells expressing a chimeric antigen receptor (CAR) against BCMA (BCMA CAR T cells), and A tissue sample obtained from the patient after the administration contained a level of sBCMA higher than 30% of the level of soluble BCMA (sBCMA) found in a tissue sample obtained from the patient before the administration. The method.

8. A method for determining whether a patient diagnosed with a disease caused by BCMA-expressing cells should undergo non-CAR T-cell therapy after treatment using immune cells expressing a chimeric antigen receptor (CAR) for B cell maturation material (BCMA CAR T cells), The process includes determining the level of soluble BCMA (sBCMA) in a tissue sample derived from the patient, The patient has previously been administered immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells), and If the level of sBCMA in the tissue sample is higher than 30% of the level of sBCMA found in the tissue sample obtained from the patient prior to the administration, then the patient is a candidate for the non-CAR T-cell therapy. The method.

9. The method according to claim 8, further comprising the step of administering the non-CAR T cell therapy to the candidate for the non-CAR T cell therapy.

10. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. The step of administering immune cells expressing a chimeric antigen receptor (CAR) against BCMA (BCMA CAR T cells) to the subject, and b. A step to determine the level of soluble BCMA (sBCMA) in a tissue sample derived from the subject. Includes, If the sBCMA level is higher than 4000 ng / L, the subject is subsequently provided with non-CAR T-cell therapy to treat the disease. The method.

11. The method according to claim 10, wherein the level of sBCMA is determined 50 to 70 days after the administration step.

12. The method according to claim 10 or 11, wherein the level of sBCMA is determined 55 to 65 days after the administration step.

13. The method according to any one of claims 10 to 12, wherein the level of sBCMA is determined 58 to 62 days after the administration step.

14. The method according to any one of claims 11 to 13, wherein the non-CAR T cell therapy is provided to the subject within 3 months, 2 months, or 1 month after the step of determining the level of sBCMA.

15. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. A step of determining the first level of interleukin-6 (IL-6), tumor necrosis factor α (TNFα), or both, in a tissue sample derived from the subject. b. The step of administering immune cells expressing a chimeric antigen receptor (CAR) against BCMA (BCMA CAR T cells) to the subject, and c. The subsequent step of determining the second levels of IL-6, TNFα, or both, in the tissue sample derived from the subject. Includes, If the second level of IL-6, TNFα, or both is not higher than the first level of IL-6, TNFα, or both, the subject is subsequently provided with non-CAR T-cell therapy to treat the disease. The method.

16. The method according to claim 15, wherein the first level is determined on the day of the step in which immune cells expressing CAR against BCMA are administered to the subject, and the second level is determined 1 to 4 days after the administration step.

17. The method according to claim 16, wherein the second level is determined two days after the administration step.

18. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. The step of administering immune cells expressing a chimeric antigen receptor (CAR) against BCMA (BCMA CAR T cells) to the subject, and b. A step to determine the level of ferritin in a tissue sample derived from the subject. Includes, If the ferritin level is higher than 1500 picomoles per liter, the subject is subsequently provided with treatment to treat cytokine release syndrome (CRS). The method.

19. The method according to claim 18, wherein the determination step is performed within 0 to 4 days prior to the administration step.

20. The method according to claim 18, wherein the determination step is performed on the same day as the administration step.

21. The method according to claim 18, wherein the treatment for treating CRS is first provided to the subject 0 to 5 days after the administration step.

22. The method according to any one of claims 1 to 21, wherein the disease caused by BCMA-expressing cells is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin lymphoma.

23. The method according to claim 22, wherein the disease caused by BCMA-expressing cells is multiple myeloma.

24. The method according to claim 23, wherein the multiple myeloma is high-risk multiple myeloma, or relapsed and refractory multiple myeloma.

25. The method according to claim 22, wherein the disease caused by BCMA-expressing cells is a non-Hodgkin lymphoma, and the non-Hodgkin lymphoma is selected from the group consisting of Burkitt lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large B-cell lymphoma, precursor B-lymphoblastic lymphoma, and mantle cell lymphoma.

26. The method according to any one of claims 1 to 25, wherein the immune cells are T cells.

27. The aforementioned immune cells are 150 × 10 6 Cell ~450×10 6 The method according to any one of claims 1 to 26, wherein the dose is administered in a cellular dose.

28. The method according to any one of claims 1 to 27, wherein, prior to the administration step, the subject has received three or more lines of prior treatment.

29. The method according to any one of claims 1 to 27, wherein, prior to the administration step, the subject has received one or more lines of prior treatment.

30. The method according to claim 28 or 29, wherein the prior treatment of the line comprises a proteasome inhibitor, lenalidomide, pomalidomide, thalidomide, bortezomib, dexamethasone, cyclophosphamide, doxorubicin, carfilzomib, ixazomib, cisplatin, doxorubicin, etoposide, the anti-CD38 antibody panobinostat, or elotuzumab.

31. The method according to claim 28 or 29, wherein, prior to the administration step, the subject has received one or more lines of prior treatment, and the one or more lines of prior treatment includes the following: a. Daratumumab, pomalidomide, and dexamethasone (DPd); b. Daratumumab, bortezomib, and dexamethasone (DVd); c. Ixazomib, lenalidomide, and dexamethasone (IRd); d. Daratumumab, lenalidomide, and dexamethasone; e. Bortezomib, lenalidomide, and dexamethasone (RVd); f. Bortezomib, cyclophosphamide, and dexamethasone (BCd); g. Bortezomib, doxorubicin, and dexamethasone; h. Carfilzomib, lenalidomide, and dexamethasone (CRd); i. Bortezomib and dexamethasone; j. Bortezomib, thalidomide, and dexamethasone; k. Lenalidomide and dexamethasone; l. Dexamethasone, thalidomide, cisplatin, doxorubici, cyclophosphamide, etoposide, and bortezomib (VTD-PACE); m. Lenalidomide and low-dose dexamethasone; n. Bortezomib, cyclophosphamide, and dexamethasone; o. Carfilzomib and dexamethasone; p. Lenalidomide alone; q. Bortezomib alone; r. Daratumumab alone; s. Elotuzumab, lenalidomide, and dexamethasone; t. Elotuzumab, lenalidomide, and dexamethasone; u. Bendamustine, bortezomib, and dexamethasone; v. Bendamustine, lenalidomide, and dexamethasone; w. Pomalidomide and dexamethasone; x. Pomalidomide, bortezomib, and dexamethasone; y. Pomalidomide, carfilzomib, and dexamethasone; z. Bortezomib and liposomal doxorubicin; aa. Cyclophosphamide, lenalidomide, and dexamethasone; bb. Elotuzumab, bortezomib, and dexamethasone; cc. Ixazomib and dexamethasone; dd. Panobinostat, bortezomib, and dexamethasone; ee. Panobinostat and carfilzomib; or ff. Pomalidomide, cyclophosphamide, and dexamethasone.

32. The method according to claim 31, wherein the subject has received two, three, four, five, six, seven, or more lines of the preceding treatment of the line.

33. The method according to claim 31, wherein the subject has received three or fewer lines of treatment prior to the line mentioned above.

34. The method according to claim 31, wherein the subject has received two or fewer lines of treatment prior to the line of treatment.

35. The method according to claim 31, wherein the subject has received one or less of the preceding treatments of the line.

36. The method according to any one of claims 1 to 35, wherein the CAR comprises an antibody or antibody fragment that targets BCMA.

37. The method according to any one of claims 1 to 36, wherein the CAR comprises a single-chain Fv antibody fragment (scFv).

38. The method according to any one of claims 1 to 36, wherein the CAR includes BCMA02 scFv.

39. The method according to any one of claims 1 to 36, wherein the immune cells are idecabtagene vicleucel cells.

40. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. A step of determining a first level of soluble BCMA (sBCMA) and / or a first level of interleukin-6 (IL-6), tumor necrosis factor α (TNFα), or both, in a tissue sample derived from the subject. b. The step of administering immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells) to the subject, and c. A step of determining the second level of sBCMA and / or the second level of interleukin-6 (IL-6), tumor necrosis factor α (TNFα), or both, in a tissue sample derived from the subject. Includes, If the second level of sBCMA is higher than 30% of the first level of sBCMA, and / or if the second level of IL-6, TNFα, or both is not higher than the first level of IL-6, TNFα, or both, the subject is subsequently provided with non-CAR T-cell therapy to treat the disease. The method.

41. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. A step of determining a first level of soluble BCMA (sBCMA) and / or a first level of interleukin-6 (IL-6), tumor necrosis factor α (TNFα), or both, in a tissue sample derived from the subject. b. A step of administering immune cells expressing a chimeric antigen receptor (CAR) against BCMA (BCMA CAR T cells) to the subject. c. A step of determining that the second level of sBCMA in a tissue sample derived from the subject is higher than 30% of the first level of sBCMA, and / or that the second level of IL-6, TNFα, or both is not higher than the first level of IL-6, TNFα, or both; d. A step of providing non-CAR T-cell therapy to the subject based on the decision made in step c. The method, including the method.

42. A method for treating diseases caused by B-cell maturation material (BCMA) expressing cells, The process includes administering non-CAR T-cell therapy to patients diagnosed with the disease, The patient had previously received immune cells expressing a chimeric antigen receptor (CAR) against BCMA (BCMA CAR T cells), and If a tissue sample from the patient after the administration contains (i) a level of sBCMA higher than 30% of the level of soluble BCMA (sBCMA) found in a tissue sample obtained from the patient prior to the administration, and / or (ii) a level of IL-6, TNFα, or both, not higher than the level of IL-6, TNFα, or both, found in a tissue sample obtained from the patient prior to the administration, The method.

43. A method for determining whether a patient diagnosed with a disease caused by BCMA-expressing cells should undergo non-CAR T-cell therapy after treatment using immune cells expressing a chimeric antigen receptor (CAR) for B cell maturation material (BCMA CAR T cells), The process includes determining the level of soluble BCMA (sBCMA) and / or the levels of IL-6, TNFα, or both, in a tissue sample derived from the patient. The patient has previously been administered immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells), and (i) If the level of sBCMA in the tissue sample is higher than 30% of the level of sBCMA found in the tissue sample obtained from the patient prior to the administration, and / or (ii) if the levels of IL-6, TNFα, or both are not higher than the levels of IL-6, TNFα, or both found in the tissue sample obtained from the patient prior to the administration, then the patient is a candidate for the non-CAR T cell therapy. The method.

44. The method according to claim 43, further comprising the step of administering the non-CAR T cell therapy to the candidate for the non-CAR T cell therapy.

45. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. A step of determining a first level of soluble BCMA (sBCMA) in a tissue sample derived from the subject, b. The step of administering immune cells expressing a chimeric antigen receptor (CAR) against BCMA (BCMA CAR T cells) to the subject, and c. A step of determining the second level of sBCMA in a tissue sample derived from the subject. Includes, If the second level of sBCMA is higher than 30% of the first level of sBCMA, the subject is subsequently administered lenalidomide to treat the disease. The method.

46. The method according to claim 45, wherein the lenalidomide is administered in a dose of approximately 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, or 25 mg.

47. The method according to claim 45, wherein the lenalidomide is administered orally at a dose of approximately 25 mg daily on days 1 to 21 of a 28-day cycle.

48. The method according to any one of claims 45 to 47, wherein the disease is multiple myeloma (MM).

49. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. A step of determining a first level of soluble BCMA (sBCMA) in a tissue sample derived from the subject, b. The step of administering immune cells expressing a chimeric antigen receptor (CAR) against BCMA (BCMA CAR T cells) to the subject, and c. A step of determining the second level of sBCMA in a tissue sample derived from the subject. Includes, If the second level of sBCMA is higher than 30% of the first level of sBCMA, the subject is subsequently administered pomalidomide to treat the disease. The method.

50. The method according to claim 49, wherein the pomalidomide is administered once daily in a dose of approximately 1 mg, 2 mg, 3 mg, or 4 mg.

51. The method according to claim 49, wherein the pomalidomide is administered orally at a dose of approximately 4 mg per day on days 1 to 21 of a 28-day cycle repeated until disease progression.

52. The method according to any one of claims 49 to 51, wherein the disease is multiple myeloma (MM).

53. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. A step of determining a first level of soluble BCMA (sBCMA) in a tissue sample derived from the subject, b. The step of administering immune cells expressing a chimeric antigen receptor (CAR) against BCMA (BCMA CAR T cells) to the subject, and c. A step of determining the second level of sBCMA in a tissue sample derived from the subject. Includes, If the second level of sBCMA is higher than 30% of the first level of sBCMA, the subject is subsequently administered CC-220 to treat the disease. The method.

54. The method according to claim 53, wherein CC-220 is administered in doses of approximately 0.15 mg, 0.3 mg, 0.45 mg, 0.6 mg, 0.75 mg, 0.9 mg, 1.0 mg, 1.1 mg, or 1.2 mg.

55. The method according to claim 53, wherein CC-220 is administered orally on days 1 to 21 of a 28-day cycle in doses of approximately 0.15 mg, 0.3 mg, 0.45 mg, 0.6 mg, 0.75 mg, 0.9 mg, 1.0 mg, 1.1 mg, or 1.2 mg daily.

56. The method according to any one of claims 53 to 55, wherein the disease is multiple myeloma (MM).

57. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. A step of determining a first level of soluble BCMA (sBCMA) in a tissue sample derived from the subject, b. The step of administering immune cells expressing a chimeric antigen receptor (CAR) against BCMA (BCMA CAR T cells) to the subject, and c. A step of determining the second level of sBCMA in a tissue sample derived from the subject. Includes, If the second level of sBCMA is higher than 30% of the first level of sBCMA, the subject is subsequently administered CC-220 and dexamethasone to treat the disease. The method.

58. The method according to claim 57, wherein CC-220 is administered in doses of approximately 0.15 mg, 0.3 mg, 0.45 mg, 0.6 mg, 0.75 mg, 0.9 mg, 1.0 mg, 1.1 mg, or 1.2 mg.

59. The method according to claim 57 or claim 58, wherein the dexamethasone is administered in a dose of approximately 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, or 60 mg.

60. The method according to claim 57, wherein CC-220 is administered orally on days 1 to 21 of a 28-day cycle in doses of approximately 0.15 mg, 0.3 mg, 0.45 mg, 0.6 mg, 0.75 mg, 0.9 mg, 1.0 mg, 1.1 mg, or 1.2 mg daily.

61. The method according to any one of claims 57 to 60, wherein the dexamethasone is administered orally on days 1, 8, 15, and 22 of a 28-day cycle in doses of approximately 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, or 60 mg.

62. The method according to any one of claims 57 to 61, wherein the disease is multiple myeloma (MM).

63. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. A step of determining a first level of soluble BCMA (sBCMA) in a tissue sample derived from the subject, b. A step of applying a first BCMA-based treatment method to the subject, which includes immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells), and c. A step of determining the second level of sBCMA in a tissue sample derived from the subject. Includes, If the second level of sBCMA is higher than 30% of the first level of sBCMA, the subject is subsequently provided with a second BCMA-based treatment for treating the disease, and The first BCMA-based treatment method and the second BCMA-based treatment method are different BCMA-based treatment methods. The method.

64. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. A step of determining a first level of soluble BCMA (sBCMA) in a tissue sample derived from the subject, b. A step of applying a first BCMA-based treatment method to the subject, which includes immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells). c. A step of determining that the second level of sBCMA in the tissue sample derived from the subject is higher than 30% of the first level of sBCMA, and d. A step of providing the subject with a second BCMA-based treatment method based on the decision made in step c. Includes, The first BCMA-based treatment method and the second BCMA-based treatment method are different BCMA-based treatment methods. The method.

65. The method according to claim 63, wherein if the second level of sBCMA is higher than 40% of the first level of sBCMA, a second BCMA-based treatment mode for treating the disease is provided to the subject.

66. The method according to any one of claims 63, 64, or 65, wherein the second level of sBCMA is determined 25 to 35 days after the process being carried out.

67. The method according to any one of claims 63, 64, or 65, wherein the second level of sBCMA is determined 28 to 31 days after the process being carried out.

68. The method according to any one of claims 63 to 67, wherein the subject is provided with a second BCMA-based treatment pattern within three months, two months, or one month after the step of determining a second level of sBCMA.

69. A method for treating diseases caused by B-cell maturation material (BCMA) expressing cells, The process includes the step of administering a second BCMA-based treatment regimen to a patient diagnosed with the disease, The patient had previously received a first BCMA-based treatment regimen that included immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells), The first BCMA-based treatment method and the second BCMA-based treatment method are different BCMA-based treatment methods, and The tissue sample obtained from the patient after the procedure contained a level of sBCMA higher than 30% of the level of soluble BCMA (sBCMA) found in the tissue sample obtained from the patient before the procedure. The method.

70. A method for determining whether a patient diagnosed with a disease caused by BCMA-expressing cells should undergo a second BCMA-based treatment after treatment with a first BCMA-based treatment regimen including immune cells expressing a chimeric antigen receptor (CAR) for B cell maturation material (BCMA CAR T cells), The first BCMA-based treatment method and the second BCMA-based treatment method are different BCMA-based treatment methods. The method includes a step of determining the level of soluble BCMA (sBCMA) in a tissue sample derived from the patient, The patient has previously undergone the first BCMA-based treatment regimen, which includes immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells), and If the level of sBCMA in the tissue sample is higher than 30% of the level of sBCMA found in the tissue sample obtained from the patient prior to the procedure, the patient is a candidate for the second BCMA-based treatment. The method.

71. The method according to claim 70, further comprising the step of performing the second BCMA-based treatment on a candidate for the second BCMA-based treatment.

72. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. A step of applying a first BCMA-based treatment method to the subject, which includes immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells), and b. A step to determine the level of soluble BCMA (sBCMA) in a tissue sample derived from the subject. Includes, If the sBCMA level is higher than 4000 ng / L, the subject is subsequently provided with a second BCMA-based treatment regimen for treating the disease, and The first BCMA-based treatment method and the second BCMA-based treatment method are different BCMA-based treatment methods. The method.

73. The method according to claim 72, wherein the level of sBCMA is determined 50 to 70 days after the process to be carried out.

74. The method according to claim 72 or 73, wherein the level of sBCMA is determined 55 to 65 days after the process to be carried out.

75. The method according to any one of claims 72 to 74, wherein the level of sBCMA is determined 58 to 62 days after the process to be carried out.

76. The method according to any one of claims 73 to 75, wherein the subject is provided with the second BCMA-based treatment method within 3 months, 2 months, or 1 month after the step of determining the level of sBCMA.

77. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. A step of determining the first level of interleukin-6 (IL-6), tumor necrosis factor α (TNFα), or both, in a tissue sample derived from the subject. b. A step of applying a first BCMA-based treatment method to the subject, which includes immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells), and c. The subsequent step of determining the second levels of IL-6, TNFα, or both, in the tissue sample derived from the subject. Includes, If the second level of IL-6, TNFα, or both is not higher than the first level of IL-6, TNFα, or both, the subject is subsequently provided with a second BCMA-based treatment mode for treating the disease, and The first BCMA-based treatment method and the second BCMA-based treatment method are different BCMA-based treatment methods. The method.

78. The method according to claim 77, wherein the first level is determined on the day of the step in which the first BCMA-based treatment mode, comprising immune cells expressing CAR against BCMA, is performed on the subject, and the second level is determined one to four days after the step in which the procedure is performed.

79. The method according to claim 78, wherein the second level is determined two days after the process to be carried out.

80. The method according to any one of claims 1 to 79, wherein the disease caused by BCMA-expressing cells is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin lymphoma.

81. The method according to claim 80, wherein the disease caused by BCMA-expressing cells is multiple myeloma.

82. The method according to claim 81, wherein the multiple myeloma is a high-risk multiple myeloma or a relapsed and refractory multiple myeloma.

83. The method according to claim 80, wherein the disease caused by BCMA-expressing cells is a non-Hodgkin lymphoma, and the non-Hodgkin lymphoma is selected from the group consisting of Burkitt lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large B-cell lymphoma, precursor B-lymphoblastic lymphoma, and mantle cell lymphoma.

84. The method according to any one of claims 1 to 83, wherein the immune cells are T cells.

85. The aforementioned immune cells are 150 × 10 6 Cell ~450×10 6 The method according to any one of claims 1 to 84, wherein the dose is administered in a cellular dose.

86. The method according to any one of claims 1 to 85, wherein, prior to the administration step, the subject has received three or more lines of prior treatment.

87. The method according to any one of claims 1 to 85, wherein, prior to the administration step, the subject has received one or more lines of prior treatment.

88. The method according to claim 86 or 87, wherein the prior treatment of the line comprises a proteasome inhibitor, lenalidomide, pomalidomide, thalidomide, bortezomib, dexamethasone, cyclophosphamide, doxorubicin, carfilzomib, ixazomib, cisplatin, doxorubicin, etoposide, the anti-CD38 antibody panobinostat, or elotuzumab.

89. The method according to claim 86 or 87, wherein, prior to the administration step, the subject has received one or more lines of prior treatment, and the one or more lines of prior treatment includes the following: a. Daratumumab, pomalidomide, and dexamethasone (DPd); b. Daratumumab, bortezomib, and dexamethasone (DVd); c. Ixazomib, lenalidomide, and dexamethasone (IRd); d. Daratumumab, lenalidomide, and dexamethasone; e. Bortezomib, lenalidomide, and dexamethasone (RVd); f. Bortezomib, cyclophosphamide, and dexamethasone (BCd); g. Bortezomib, doxorubicin, and dexamethasone; h. Carfilzomib, lenalidomide, and dexamethasone (CRd); i. Bortezomib and dexamethasone; j. Bortezomib, thalidomide, and dexamethasone; k. Lenalidomide and dexamethasone; l. Dexamethasone, thalidomide, cisplatin, doxorubici, cyclophosphamide, etoposide, and bortezomib (VTD-PACE); m. Lenalidomide and low-dose dexamethasone; n. Bortezomib, cyclophosphamide, and dexamethasone; o. Carfilzomib and dexamethasone; p. Lenalidomide alone; q. Bortezomib alone; r. Daratumumab alone; s. Elotuzumab, lenalidomide, and dexamethasone; t. Elotuzumab, lenalidomide, and dexamethasone; u. Bendamustine, bortezomib, and dexamethasone; v. Bendamustine, lenalidomide, and dexamethasone; w. Pomalidomide and dexamethasone; x. Pomalidomide, bortezomib, and dexamethasone; y. Pomalidomide, carfilzomib, and dexamethasone; z. Bortezomib and liposomal doxorubicin; aa. Cyclophosphamide, lenalidomide, and dexamethasone; bb. Elotuzumab, bortezomib, and dexamethasone; cc. Ixazomib and dexamethasone; dd. Panobinostat, bortezomib, and dexamethasone; ee. Panobinostat and carfilzomib; or ff. Pomalidomide, cyclophosphamide, and dexamethasone.

90. The method according to claim 89, wherein the subject has received two, three, four, five, six, seven, or more lines of the preceding treatment of the line.

91. The method according to claim 89, wherein the subject has received three or fewer lines of treatment prior to the line of treatment.

92. The method according to claim 89, wherein the subject has received two or fewer lines of treatment prior to the line of treatment.

93. The method according to claim 89, wherein the subject has received one or less of the preceding treatments of the line.

94. The method according to any one of claims 1 to 93, wherein the CAR comprises an antibody or antibody fragment that targets BCMA.

95. The method according to any one of claims 1 to 94, wherein the CAR comprises a single-chain Fv antibody fragment (scFv).

96. The method according to any one of claims 1 to 94, wherein the CAR includes BCMA02 scFv.

97. The method according to any one of claims 1 to 94, wherein the immune cells are idecabtagene vicleucel cells.

98. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. A step of determining a first level of soluble BCMA (sBCMA) and / or a first level of interleukin-6 (IL-6), tumor necrosis factor α (TNFα), or both, in a tissue sample derived from the subject. b. A step of applying a first BCMA-based treatment method to the subject, which includes immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells), and c. A step of determining the second level of sBCMA and / or the second level of interleukin-6 (IL-6), tumor necrosis factor α (TNFα), or both, in a tissue sample derived from the subject. Includes, If the second level of sBCMA is higher than 30% of the first level of sBCMA, and / or if the second level of IL-6, TNFα, or both is not higher than the first level of IL-6, TNFα, or both, then the subject is subsequently provided with a second BCMA-based treatment for treating the disease, and The first BCMA-based treatment method and the second BCMA-based treatment method are different BCMA-based treatment methods. The method.

99. A method for treating diseases caused by B-cell maturation substance (BCMA) expressing cells in subjects where such treatment is necessary, a. A step of determining a first level of soluble BCMA (sBCMA) and / or a first level of interleukin-6 (IL-6), tumor necrosis factor α (TNFα), or both, in a tissue sample derived from the subject. b. A step of applying a first BCMA-based treatment method to the subject, which includes immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells). c. A step of determining that the second level of sBCMA in a tissue sample derived from the subject is higher than 30% of the first level of sBCMA, and / or that the second level of IL-6, TNFα, or both is not higher than the first level of IL-6, TNFα, or both; d. A step of providing the subject with a second BCMA-based treatment method based on the decision made in step c. Includes, The first BCMA-based treatment method and the second BCMA-based treatment method are different BCMA-based treatment methods. The method.

100. A method for treating diseases caused by B-cell maturation material (BCMA) expressing cells, The process includes the step of administering a second BCMA-based treatment regimen to a patient diagnosed with the disease, The patient had previously received a first BCMA-based treatment regimen that included immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells), The first BCMA-based treatment method and the second BCMA-based treatment method are different BCMA-based treatment methods, and If a tissue sample from the patient after the procedure contains (i) a level of sBCMA higher than 30% of the level of soluble BCMA (sBCMA) found in a tissue sample obtained from the patient before the procedure, and / or (ii) a level of IL-6, TNFα, or both, not higher than the level of IL-6, TNFα, or both, found in a tissue sample obtained from the patient before the procedure, The method.

101. A method for determining whether a patient diagnosed with a disease caused by BCMA-expressing cells should undergo a second BCMA-based treatment after treatment with a first BCMA-based treatment regimen including immune cells expressing a chimeric antigen receptor (CAR) for B cell maturation material (BCMA CAR T cells), The process includes determining the level of soluble BCMA (sBCMA) and / or the levels of IL-6, TNFα, or both, in a tissue sample derived from the patient. The patient had previously undergone the first BCMA-based treatment regimen, which included immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells). (i) if the level of sBCMA in the tissue sample is higher than 30% of the level of sBCMA found in the tissue sample obtained from the patient prior to the procedure, and / or (ii) if the level of IL-6, TNFα, or both is not higher than the level of IL-6, TNFα, or both found in the tissue sample obtained from the patient prior to the procedure, then the patient is a candidate for the second BCMA-based treatment, and The first BCMA-based treatment method and the second BCMA-based treatment method are different BCMA-based treatment methods. The method.

102. The method according to claim 101, further comprising the step of performing the second BCMA-based treatment on a candidate for the second BCMA-based treatment.

103. The method according to any one of claims 63 to 102, wherein the second BCMA-based treatment mode comprises a BCMA antibody-drug conjugate (ADC), a bispecific T cell engager (BiTE) targeting B-cell maturation antigen (BCMA), a natural killer (NK) cell engager (NKCE) targeting B-cell maturation antigen (BCMA), or immune cells expressing a chimeric antigen receptor (CAR) against BCMA (BCMA CAR T cells).

104. The method according to claim 103, wherein the second BCMA-based treatment mode comprises a BCMA antibody-drug conjugate (ADC).

105. The method according to claim 104, wherein the BCMA antibody-drug conjugate (ADC) comprises CC99712 or GSK2857916 (verantamab mafodotin).

106. The method according to claim 103, wherein the second BCMA-based treatment mode comprises a bispecific T cell engager (BiTE) that targets a B cell maturation antigen (BCMA).

107. The method according to claim 106, wherein the bispecific T cell engager (BiTE) targeting a B cell maturation antigen (BCMA) includes CC-93269, AMG 420, JNJ-64007957, AMG 701, PF-06863135, REGN5458, REGN5459, or TNB-383B.

108. The method according to claim 103, wherein the second BCMA-based treatment mode comprises a natural killer (NK) cell engager (NKCE) that targets a B cell maturation antigen (BCMA).

109. The method according to claim 108, wherein the natural killer (NK) cell engager (NKCE) that targets a B cell maturation antigen (BCMA) comprises DF3001, AFM26, CTX-4419, or CTX-8573.

110. The method according to claim 103, wherein the second BCMA-based treatment mode comprises immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells).

111. The method according to claim 103 or 110, wherein the immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells) include JCARH125, KITE-585, P-BCMA-101, LCAR-B38M, CT053, anti-CD19 / BCMA CAR-T cells, and CTX120.

112. The method according to any one of claims 98 to 111, wherein the immune cells in the first BCMA-based treatment mode, which include immune cells expressing a chimeric antigen receptor (CAR) for BCMA (BCMA CAR T cells), are idecabtagene vicleucel cells.

113. The method according to any one of claims 63 to 112, wherein the second BCMA-based treatment method does not include idecabtagene vicleucel cells.

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