RU2025102601A - COMBINATIONS OF HETERODIMERIC Fc-FUSION PROTEINS IL15/IL15Rα AND BISPECIFIC ANTIBODIES FcRH5xCD3 FOR THE TREATMENT OF BLOOD CANCER TYPES - Google Patents

Claims (91)

1. A method for treating blood cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of (a) a heterodimeric IL15-IL15Rα Fc fusion protein and (b) an FcRH5xCD3 bispecific antibody or fragment thereof that binds both antigens. 2. Use of a therapeutically effective amount of (a) a heterodimeric IL15-IL15Rα Fc fusion protein and (b) an FcRH5xCD3 bispecific antibody or fragment thereof that binds both antigens in the manufacture of one or more medicinal products for the treatment of blood cancer in a subject in need thereof. 3. A therapeutically effective amount of (a) a heterodimeric IL15-IL15Rα Fc fusion protein and (b) an FcRH5xCD3 bispecific antibody or fragment thereof that binds both antigens, for use in the treatment of blood cancer in a subject in need thereof. 4. The method according to claim 1, the use according to claim 2, or a heterodimeric IL15-IL15Rα Fc fusion protein and an FcRH5xCD3 bispecific antibody or fragment thereof according to claim 3, wherein the heterodimeric IL15-IL15Rα Fc fusion protein comprises: (a) a first fusion protein comprising an interleukin-15 (IL-15) protein covalently linked to the N-terminus of a first Fc domain via a first domain linker, wherein the IL-15 protein comprises the amino acid sequence of SEQ ID NO: 5 and wherein the first Fc domain is a variant of the human IgG1 Fc domain; and (b) a second fusion protein comprising a fragment of the IL-15 alpha receptor protein (IL-15Rα) covalently linked to the N-terminus of a second Fc domain via a second domain linker, wherein the IL-15Rα protein comprises the amino acid sequence of SEQ ID NO: 4, and wherein the second Fc domain is a variant of the human IgG1 Fc domain. 5. The method, use or heterodimeric IL15-IL15Rα Fc fusion protein and the FcRH5xCD3 bispecific antibody or fragment thereof according to claim 4, wherein the heterodimeric IL15-IL15Rα Fc fusion protein comprises: (a) a first fusion protein comprising an interleukin-15 (IL-15) protein covalently linked to the N-terminus of a first Fc domain via a first domain linker, wherein the IL-15 protein comprises the amino acid sequence of SEQ ID NO: 5, and wherein the first Fc domain comprises the amino acid sequence of SEQ ID NO: 6; and (b) a second fusion protein comprising a fragment of an IL-15 alpha receptor protein (IL-15Rα) covalently linked to the N-terminus of a second Fc domain via a second domain linker, wherein the IL-15Rα protein comprises the amino acid sequence of SEQ ID NO: 4, and wherein the second Fc domain comprises the amino acid sequence of SEQ ID NO: 7. 6. The method according to any one of claims 4-5, the use according to any one of claims 4-5, or the heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 4-5, wherein the linker of the first domain comprises the amino acid sequence of SEQ ID NO: 8. 7. The method according to any one of claims 4-6, the use according to any one of claims 4-6, or the heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 4-6, wherein the linker of the second domain comprises the amino acid sequence of SEQ ID NO: 8. 8. The method according to any one of claims 4-7, the use according to any one of claims 4-7, or the heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 4-7, wherein the linker of the first domain comprises the amino acid sequence of SEQ ID NO: 8, and the linker of the second domain comprises the amino acid sequence of SEQ ID NO: 8. 9. The method according to any one of claims 4-8, the use according to any one of claims 4-8, or a heterodimeric Fc fusion protein IL15-IL15Rα and a bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 4-8, wherein the first fusion protein comprises the amino acid sequence SEQ ID NO: 9. 10. The method according to any one of claims 4-9, the use according to any one of claims 4-9, or the heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 4-9, wherein the second fusion protein comprises the amino acid sequence of SEQ ID NO: 10. 11. The method according to any one of claims 1 and 4-10, the use according to any one of claims 2 and 4-10, or the heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 3-10, wherein the heterodimeric protein comprises a first fusion protein comprising the amino acid sequence presented in SEQ ID NO: 9, and the second fusion protein comprises the amino acid sequence presented in SEQ ID NO: 10. 12. The method according to any one of claims 1 and 4-11, the use according to any one of claims 2 and 4-11, or the heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 3-11, wherein the heterodimeric Fc fusion protein IL15-IL15Rα is XmAb24306. 13. The method according to any one of claims 1 and 4-12, the use according to any one of claims 2 and 4-12, or the heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 3-12, wherein the bispecific antibody FcRH5xCD3 or fragment thereof that binds both antigens comprises a light chain variable region to FcRH5, a heavy chain variable region to FcRH5, a light chain variable region to CD3 and a heavy chain variable region to CD3. 14. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 13, wherein the variable region of the light chain to FcRH5 comprises a light chain complementarity determining region-1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 11, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 12, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 13; and the FcRH5 heavy chain variable region comprises a heavy chain complementarity determining region-1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 14, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 15, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 16. 15. A method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and a bispecific antibody FcRH5xCD3 or a fragment thereof according to claim 13 or claim 14, wherein the variable region of the light chain to FcRH5 comprises the amino acid sequence of SEQ ID NO: 17. 16. A method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and a bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 13-15, wherein the variable region of the heavy chain to FcRH5 comprises the amino acid sequence of SEQ ID NO: 18. 17. A method, use or heterodimeric Fc fusion protein IL15-IL15Rα and a bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 13-16, wherein the light chain to FcRH5 comprises the amino acid sequence of SEQ ID NO: 19. 18. A method, use or heterodimeric Fc fusion protein IL15-IL15Rα and a bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 13-17, wherein the heavy chain to FcRH5 comprises the amino acid sequence of SEQ ID NO: 20. 19. A method, use or heterodimeric Fc fusion protein of IL15-IL15Rα and a bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 13-18, wherein the variable region of the light chain to CD3 comprises a light chain complementarity determining region-1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 21, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 22, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 23; and the anti-CD3 heavy chain variable region comprises a heavy chain complementarity determining region-1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 24, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 25, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 26. 20. A method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and a bispecific antibody FcRH5xCD3 or a fragment thereof according to claim 19, wherein the variable region of the light chain to CD3 comprises the amino acid sequence of SEQ ID NO: 27. 21. A method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and a bispecific antibody FcRH5xCD3 or a fragment thereof according to claim 19 or claim 20, wherein the variable region of the heavy chain to CD3 comprises the amino acid sequence of SEQ ID NO: 28. 22. A method, use or heterodimeric Fc fusion protein IL15-IL15Rα and a bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 19-21, wherein the light chain to CD3 comprises the amino acid sequence of SEQ ID NO: 29. 23. The method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 19-22, wherein the heavy chain to CD3 comprises the amino acid sequence of SEQ ID NO: 30. 24. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 19-23, wherein the variable region of the light chain to FcRH5 comprises the amino acid sequence of SEQ ID NO: 17; the variable region of the heavy chain to FcRH5 comprising the amino acid sequence of SEQ ID NO: 18, the variable region of the light chain to CD3 comprising the amino acid sequence of SEQ ID NO: 27, and the variable region of the heavy chain to CD3 comprising the amino acid sequence of SEQ ID NO: 28. 25. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 19-24, wherein the light chain to FcRH5 comprises the amino acid sequence of SEQ ID NO: 19; the heavy chain to FcRH5 comprises the amino acid sequence of SEQ ID NO: 20; the light chain to CD3 comprises the amino acid sequence of SEQ ID NO: 29; and the light chain to CD3 comprises the amino acid sequence of SEQ ID NO: 30. 26. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 19-25, wherein the bispecific antibody FcRH5xCD3 is cevostamab. 27. The method according to any one of claims 1 and 4-26, the use according to any one of claims 2 and 4-26, or the heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 3-26, wherein said blood cancer is selected from the group consisting of leukemia, acute myeloid leukemia, adult acute lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma, non-Hodgkin's lymphoma, B-cell non-Hodgkin's lymphoma and multiple myeloma. 28. The method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or a fragment thereof according to claim 27, wherein said blood cancer is multiple myeloma. 29. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 28, wherein said multiple myeloma is relapsed or refractory multiple myeloma. 30. The method according to any one of claims 1 and 4-29, the use according to any one of claims 2 and 4-29, or the heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 3-29, wherein the subject has previously been administered one or more previous treatment options. 31. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and bispecific antibody FcRH5xCD3 or fragment thereof according to claim 30, wherein the previous treatment option is an immunomodulatory drug, a proteasome inhibitor or a monoclonal antibody to CD38. 32. The method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or a fragment thereof according to claim 31, wherein the immunomodulatory drug is selected from the group consisting of lenalidomide, thalidomide and pomalidomide. 33. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 31, wherein the proteasome inhibitor is selected from the group consisting of bortezomib, carfilzomib and ixazomib. 34. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or a fragment thereof according to claim 31, wherein the monoclonal antibody to CD38 is selected from the group consisting of daratumumab, isatuximab, mesagitamab and felzartamab. 35. The method according to any one of claims 1 and 4-33, the use according to any one of claims 2 and 4-34, or the heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 3-34, wherein the IL15-IL15Rα heterodimeric Fc fusion protein is administered at a dose selected from the group consisting of about 0.0025 mg/kg, about 0.005 mg/kg, about 0.01 mg/kg, about 0.015 mg/kg, about 0.02 mg/kg, about 0.025 mg/kg, about 0.03 mg/kg, about 0.04 mg/kg, about 0.05 mg/kg, about 0.06 mg/kg, about 0.08 mg/kg, about 0.1 mg/kg, about 0.12 mg/kg, about 0.16 mg/kg, about 0.2 mg/kg, about 0.24 mg/kg and about 0.32 mg/kg body weight. 36. The method, use, or heterodimeric IL15-IL15Rα Fc fusion protein and the FcRH5xCD3 bispecific antibody or fragment thereof according to claim 35, wherein the heterodimeric IL15-IL15Rα Fc fusion protein is administered at a dose selected from the group consisting of about 0.01 mg/kg, about 0.02 mg/kg, about 0.04 mg/kg, about 0.06 mg/kg, about 0.09 mg/kg, and about 0.12 mg/kg body weight. 37. The method according to any one of claims 1 and 4-36, the use according to any one of claims 2 and 4-36, or the heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 3-36, wherein the heterodimeric IL15-IL15Rα Fc fusion protein is administered at a dose selected from the group consisting of 0.0025 mg/kg, 0.005 mg/kg, 0.01 mg/kg, 0.015 mg/kg, 0.02 mg/kg, 0.025 mg/kg, 0.03 mg/kg, 0.04 mg/kg, 0.05 mg/kg, 0.06 mg/kg, 0.08 mg/kg, 0.10 mg/kg, 0.16 mg/kg, 0.20 mg/kg, 0.24 mg/kg and 0.32 mg/kg body weight. 38. The method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 36, wherein the heterodimeric Fc-fusion protein IL15-IL15Rα is administered at a dose selected from the group consisting of 0.01 mg/kg, 0.02 mg/kg, 0.04 mg/kg, 0.06 mg/kg, 0.09 mg/kg and 0.12 mg/kg body weight. 39. The method according to any one of claims 1 and 4-38, the use according to any one of claims 2 and 4-38, or the heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 3-38, wherein the heterodimeric Fc-fusion protein IL15-IL15Rα is administered at a frequency selected from the group consisting of k1n, k2n, k3n, k4n, k5n and k6n. 40. The method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and bispecific antibody FcRH5xCD3 or a fragment thereof according to claim 39, wherein the heterodimeric Fc-fusion protein IL15-IL15Rα is administered at a frequency of k1n during one or more cycles. 41. The method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and bispecific antibody FcRH5xCD3 or a fragment thereof according to claim 39, wherein the heterodimeric Fc-fusion protein IL15-IL15Rα is administered at a frequency of k2n during one or more cycles. 42. The method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and bispecific antibody FcRH5xCD3 or a fragment thereof according to claim 39, wherein the heterodimeric Fc-fusion protein IL15-IL15Rα is administered at a frequency of k4n during one or more cycles. 43. The method according to any one of claims 1 and 4-42, the use according to any one of claims 2 and 4-42, or the heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 3-42, wherein the heterodimeric Fc-fusion protein IL15-IL15Rα is administered intravenously. 44. The method according to any one of claims 1 and 4-43, the use according to any one of claims 2 and 4-43, or the heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 3-43, wherein the heterodimeric Fc-fusion protein IL15-IL15Rα and said bispecific antibody FcRH5xCD3 or a fragment thereof that binds both antigens are administered simultaneously. 45. The method according to any one of claims 1 and 4-43, the use according to any one of claims 2 and 4-43, or the heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 3-43, wherein the heterodimeric Fc-fusion protein IL15-IL15Rα and the said bispecific antibody FcRH5xCD3 or a fragment thereof that binds both antigens are administered sequentially. 46. The method according to any one of claims 1 and 4-45, the use according to any one of claims 2 and 4-43, or the heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 3-43, wherein said bispecific antibody FcRH5xCD3 or fragment thereof that binds both antigens is administered at a frequency selected from the group consisting of k1n, k2n, k3n, k4n, k5n and k6n, during one or more cycles. 47. The method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 46, wherein said bispecific antibody FcRH5xCD3 or fragment thereof that binds both antigens is administered at a frequency of k2n during one or more cycles. 48. The method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and bispecific antibody FcRH5xCD3 or fragment thereof according to claim 47, wherein said heterodimeric Fc-fusion protein IL15-IL15Rα is administered with a frequency of k4n, and wherein said bispecific antibody FcRH5xCD3 or fragment thereof that binds both antigens is administered with a frequency of k2n during one or more cycles. 49. The method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 46, wherein said bispecific antibody FcRH5xCD3 or fragment thereof that binds both antigens is administered at a frequency of k4n during one or more cycles. 50. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 40-49, wherein each of the one or more cycles is a four-week cycle. 51. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 50, wherein the bispecific antibody FcRH5xCD3 or fragment thereof that binds both antigens is administered to 2n for six four-week cycles and is administered to 4n in the seventh and any subsequent four-week cycle. 52. The method, use, or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 51, wherein the bispecific antibody FcRH5xCD3 or fragment thereof that binds both antigens is administered on days 1 and 15 for six four-week cycles and is administered on day 1 in the seventh and any subsequent four-week cycle. 53. The method according to any one of claims 1 and 4-52, the use according to any one of claims 2 and 4-52, or the heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 3-52, wherein the bispecific antibody FcRH5xCD3 is administered at a dose of from about 132 mg to about 198 mg. 54. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 53, wherein the bispecific antibody FcRH5xCD3 is administered at a dose of about 132 mg. 55. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 54, wherein the bispecific antibody FcRH5xCD3 is administered at a dose of about 132 mg at a frequency of k2n during one or more 28-day cycles. 56. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or a fragment thereof according to claim 53, wherein the bispecific antibody FcRH5xCD3 is administered at a dose of about 160 mg. 57. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 53, wherein the bispecific antibody FcRH5xCD3 is administered at a dose of about 198 mg. 58. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 46-57, wherein one or more boosted initial doses of the bispecific antibody FcRH5xCD3 or fragment thereof that binds both antigens are administered to the subject during the preliminary phase prior to the first treatment cycle. 59. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 58, wherein the preliminary phase is seven days. 60. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 58 or 59, wherein the boosted initial dose of the bispecific antibody FcRH5xCD3 is about 3.6 mg. 61. A method, use, or heterodimeric IL15-IL15Rα Fc fusion protein and an FcRH5xCD3 bispecific antibody or fragment thereof according to any one of claims 58-60, wherein the subject is administered two boosted initial doses of the FcRH5xCD3 bispecific antibody or fragment thereof that binds both antigens. 62. The method, use, or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 61, wherein the first boosted initial dose is administered on day 1 of the preliminary phase. 63. The method, use, or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 62, wherein the second boosted initial dose is administered between days 2-4 of the preliminary phase. 64. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 61-63, wherein the minimum interval between the end of the first boosted initial dose and the start of the second boosted initial dose is 20 hours. 65. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 61-64, wherein about 3.6 mg of the bispecific antibody FcRH5xCD3 is administered between the two boosted initial doses. 66. The method, use, or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to claim 65, wherein the first boosted initial dose is about 0.3 mg and the second boosted initial dose is about 3.3 mg. 67. The method according to any one of claims 1 and 4-55 and 58-66, the use according to any one of claims 2 and 4-55 and 58-66, or the heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 3-55 and 58-66, wherein the subject is administered a first boosted starting dose of about 0.3 mg of the FcRH5xCD3 bispecific antibody on day 1 of the preliminary phase, a second boosted starting dose of about 3.3 mg of the FcRH5xCD3 bispecific antibody between days 2-4 of the preliminary phase, and then at a dose of about 132 mg of the FcRH5xCD3 bispecific antibody on days 1 and 15 for six four-week cycles and on day 1 for the seventh and any subsequent four-week cycles. 68. The method according to any one of claims 1 and 4-67, the use according to any one of claims 2 and 4-67, or the heterodimeric Fc-fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 3-67, wherein said bispecific antibody FcRH5xCD3 is administered intravenously. 69. The method according to any one of claims 1 and 4-68, the use according to any one of claims 2 and 4-68, or the heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 3-68, wherein the method further comprises administering to the subject a therapeutically effective amount of tocilizumab. 70. The method of claim 69, wherein the subject suffers from the phenomenon of cytokine release syndrome (CRS). 71. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and bispecific antibody FcRH5xCD3 or fragment thereof according to claim 69 or 70, wherein tocilizumab is administered to subjects who remain refractory to corticosteroid 24 hours after the first dose of corticosteroid. 72. The method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 69-71, wherein tocilizumab is administered at a dose of 8 mg/kg. 73. The method, use or heterodimeric Fc fusion protein of IL15-IL15Rα and FcRH5xCD3 bispecific antibody or fragment thereof according to claim 72, wherein tocilizumab is administered at a dose of 8 mg/kg if the subject's body weight is ≥ 30 kg. 74. The method, use or heterodimeric Fc-fusion protein IL15-IL15Rα and bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 69-71, wherein tocilizumab is administered at a dose of 12 mg/kg. 75. The method, use or heterodimeric Fc-fusion protein of IL15-IL15Rα and FcRH5xCD3 bispecific antibody or fragment thereof according to claim 74, wherein tocilizumab is administered at a dose of 12 mg/kg if the patient's body weight is < 30 kg. 76. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and the bispecific antibody FcRH5xCD3 or a fragment thereof according to any one of claims 69-75, wherein tocilizumab is administered intravenously. 77. The method, use or heterodimeric Fc fusion protein IL15-IL15Rα and bispecific antibody FcRH5xCD3 or fragment thereof according to any one of claims 69-76, wherein tocilizumab is administered every 8 hours. 78. A method of treating multiple myeloma in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of (a) XmAb24306, wherein XmAb24306 comprises a first monomer comprising the amino acid sequence of SEQ ID NO: 9 and a second monomer comprising the amino acid sequence of SEQ ID NO: 10, and (b) cevostamab, wherein cevostamab comprises an anti-FcRH5 light chain comprising the amino acid sequence of SEQ ID NO: 19, an anti-FcRH5 heavy chain comprising the amino acid sequence of SEQ ID NO: 20, an anti-CD3 light chain comprising the amino acid sequence of SEQ ID NO: 29, and a CD3 heavy chain comprising the amino acid sequence of SEQ ID NO: 30, wherein XmAb24306 is administered intravenously at a dose of from about 0.02 mg/kg to about 0.06 mg/kg, and cevostamab is administered intravenously at a dose of approximately 132 mg. 79. Use of a therapeutically effective amount of (a) XmAb24306, wherein XmAb24306 comprises a first monomer comprising the amino acid sequence of SEQ ID NO: 9 and a second monomer comprising the amino acid sequence of SEQ ID NO: 10, and (b) cevostamab, wherein cevostamab comprises an α-FcRH5 light chain comprising the amino acid sequence of SEQ ID NO: 19, an α-FcRH5 heavy chain comprising the amino acid sequence of SEQ ID NO: 20, an α-CD3 light chain comprising the amino acid sequence of SEQ ID NO: 29, and a α-CD3 heavy chain comprising the amino acid sequence of SEQ ID NO: 30, in the manufacture of one or more medicaments for the treatment of multiple myeloma in a subject in need thereof, wherein XmAb24306 is formulated for intravenous administration at a dose of from about 0.02 mg/kg to about 0.06 mg/kg, and cevostamab is formulated for intravenous administration at a dose of approximately 132 mg. 80. A therapeutically effective amount of (a) XmAb24306, wherein XmAb24306 comprises a first monomer comprising the amino acid sequence of SEQ ID NO: 9 and a second monomer comprising the amino acid sequence of SEQ ID NO: 10, and (b) cevostamab, wherein cevostamab comprises an α-FcRH5 light chain comprising the amino acid sequence of SEQ ID NO: 19, an α-FcRH5 heavy chain comprising the amino acid sequence of SEQ ID NO: 20, an α-CD3 light chain comprising the amino acid sequence of SEQ ID NO: 29, and a α-CD3 heavy chain comprising the amino acid sequence of SEQ ID NO: 30, for use in the treatment of multiple myeloma in a subject in need thereof, wherein XmAb24306 is administered intravenously at a dose of from about 0.02 mg/kg to about 0.06 mg/kg, and cevostamab is administered intravenously at a dose of about 132 mg. 81. The method of claim 78, the use of claim 79, or XmAb24306 and cevostamab of claim 80, wherein the treatment further comprises administering to the subject one or more boosted starting doses of cevostamab at a total dose of about 3.6 mg during a seven-day pre-treatment phase prior to the first treatment cycle, wherein the boosted starting dose is administered as a single dose. 82. The method of claim 78, the use of claim 79, or XmAb24306 and cevostamab of claim 80, wherein the treatment further comprises administering to the subject one or more boosted initial doses of cevostamab at a total dose of about 3.6 mg during a seven-day preliminary phase prior to the first treatment cycle, wherein the boosted initial dose is administered as two doses. 83. The method, use, or XmAb24306 and cevostamab of claim 82, wherein the first boosted starting dose is about 0.3 mg and the second boosted starting dose is about 3.3 mg. 84. The method, use, or XmAb24306 and cevostamab of claim 83, wherein the first boosted initial dose is administered on day 1 of the preliminary phase, and the second boosted initial dose is administered on day 2, 3, or 4 of the preliminary phase. 85. The method according to any one of claims 78 and 81-84, the use according to any one of claims 79 and 81-84, or XmAb24306 and cevostamab according to any one of claims 80-84, wherein XmAb24306 is administered at a frequency of k4n for one or more cycles. 86. The method according to any one of claims 78 and 81-85, the use according to any one of claims 79 and 81-85, or XmAb24306 and cevostamab according to any one of claims 80-85, wherein cevostamab is administered at a frequency of k2n for one or more cycles. 87. The method according to any one of claims 78 and 81-86, the use according to any one of claims 79 and 81-86, or XmAb24306 and cevostamab according to any one of claims 80-86, wherein cevostamab is administered at a frequency of k4n for one or more cycles. 88. The method according to any one of claims 78 and 81-87, the use according to any one of claims 79 and 81-87, or XmAb24306 and cevostamab according to any one of claims 80-87, wherein XmAb24306 is administered intravenously at a frequency of k4n for at least seven four-week cycles, and wherein a first boosted starting dose of 0.3 mg of cevostamab is administered intravenously on day 1 of the preliminary phase, a second boosted starting dose of 3.3 mg of cevostamab is administered intravenously between days 2-4 of the preliminary phase, wherein the preliminary phase is seven days, and thereafter at a dose of 132 mg of cevostamab is administered intravenously on days 1 and 15 for six four-week cycles and on day 1 for the seventh and any subsequent four-week cycles. 89. A method of treating multiple myeloma in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of (a) XmAb24306, wherein XmAb24306 comprises a first monomer comprising the amino acid sequence of SEQ ID NO: 9 and a second monomer comprising the amino acid sequence of SEQ ID NO: 10, and (b) cevostamab, wherein cevostamab comprises an anti-FcRH5 light chain comprising the amino acid sequence of SEQ ID NO: 19, an anti-FcRH5 heavy chain comprising the amino acid sequence of SEQ ID NO: 20, an anti-CD3 light chain comprising the amino acid sequence of SEQ ID NO: 29, and a CD3 heavy chain comprising the amino acid sequence of SEQ ID NO: 30, wherein XmAb24306 is administered intravenously at a dose of from about 0.02 mg/kg to about 0.06 mg/kg at a frequency of q4n for at least seven four-week cycles, with the first boosted starting dose of 0.3 mg cevostamab administered intravenously on Day 1 of the preliminary phase, the second boosted starting dose of 3.3 mg cevostamab administered intravenously between Days 2-4 of the preliminary phase, with the preliminary phase period being seven days, and thereafter at a dose of 132 mg cevostamab administered intravenously on Days 1 and 15 for six four-week cycles and on Day 1 for the seventh and any subsequent four-week cycles. 90. Use of a therapeutically effective amount of (a) XmAb24306, wherein XmAb24306 comprises a first monomer comprising the amino acid sequence of SEQ ID NO: 9 and a second monomer comprising the amino acid sequence of SEQ ID NO: 10, and (b) cevostamab, wherein cevostamab comprises an α-FcRH5 light chain comprising the amino acid sequence of SEQ ID NO: 19, an α-FcRH5 heavy chain comprising the amino acid sequence of SEQ ID NO: 20, an α-CD3 light chain comprising the amino acid sequence of SEQ ID NO: 29, and a α-CD3 heavy chain comprising the amino acid sequence of SEQ ID NO: 30, in the manufacture of one or more medicaments for the treatment of multiple myeloma in a subject in need thereof, wherein XmAb24306 is formulated for intravenous administration at a dose of from about 0.02 mg/kg to about 0.06 mg/kg at a frequency of q4n for at least seven four-week cycles, wherein cevostamab is formulated to be administered intravenously at a dose of 132 mg on days 1 and 15 for six four-week cycles and on day 1 for the seventh and any subsequent four-week cycles; and wherein the treatment further includes a seven-day lead-in phase in which a first boosted starting dose of 0.3 mg cevostamab is administered intravenously on day 1 of the lead-in phase and a second boosted starting dose of 3.3 mg cevostamab is administered intravenously between days 2-4 of the lead-in phase. 91. A therapeutically effective amount of (a) XmAb24306, wherein XmAb24306 comprises a first monomer comprising the amino acid sequence of SEQ ID NO: 9 and a second monomer comprising the amino acid sequence of SEQ ID NO: 10, and (b) cevostamab, wherein cevostamab comprises an α-FcRH5 light chain comprising the amino acid sequence of SEQ ID NO: 19, an α-FcRH5 heavy chain comprising the amino acid sequence of SEQ ID NO: 20, an α-CD3 light chain comprising the amino acid sequence of SEQ ID NO: 29, and a α-CD3 heavy chain comprising the amino acid sequence of SEQ ID NO: 30, for use in the treatment of multiple myeloma in a subject in need thereof, wherein XmAb24306 is administered intravenously at a dose of from about 0.02 mg/kg to about 0.06 mg/kg at a frequency of q4n for at least seven four-week cycles, with a first boosted starting dose of 0.3 mg cevostamab administered intravenously on day 1 of the preliminary phase, a second boosted starting dose of 3.3 mg cevostamab administered intravenously between days 2-4 of the preliminary phase, with the preliminary phase being seven days, and thereafter at a dose of 132 mg cevostamab administered intravenously on days 1 and 15 for six four-week cycles and on day 1 of the seventh and any subsequent four-week cycles.