USE OF ISATUXIMAB IN COMBINATION WITH OTHER AGENTS FOR THE TREATMENT OF MULTIPLE MYELOMA

Claims

1. Use of an antibody to CD38 for the treatment of multiple myeloma, where an anti-CD38 antibody is administered to the individual in combination with an interleukin-2 analogue (IL-2 analogue), wherein the anti-CD38 antibody is administered on days 1, 8, 15, and 22 of the first 28-day cycle, and then administered on days 1 and 15 of the 28-day cycle for at least one additional cycle, and the individual is administered an IL-2 analogue, where the IL-2 analogue is administered once every two weeks or once every three weeks.

2. The use according to claim 1, wherein the antibody to CD38 is isatuximab and is administered intravenously at a dose of 10 mg / kg.

3. The use according to claim 1, wherein the antibody to CD-38 is isatuximab and is administered subcutaneously at a dose of 1400 mg.

4. The use according to any one of claims 1-3, wherein the IL-2 analogue comprises the unnatural amino acid N6-((2-azidoethoxy)-carbonyl)-L-lysine (AzK), and wherein AzK is PEGylated.

5. Use according to item 1, wherein the IL-2 analogue is administered at a dose of 16 mcg / kg, 24 mcg / kg or 32 mcg / kg.

6. The use according to any one of claims 1-3 or 5, wherein the antibody to CD38 is administered on days 1 and 15 of a 28-day cycle for at least 11 cycles and then administered on day 1 of a 28-day cycle for one or more additional cycles.

7. The use according to any one of claims 1-3 or claim 5, wherein the individual has received one or more lines of therapy for the treatment of multiple myeloma prior to receiving the first cycle of treatment, wherein the one or more previous lines of therapy comprise an anti-CD38 antibody drug and an anti-BCMA antibody drug.

8. Use of an antibody to CD38 for the treatment of multiple myeloma, where an antibody to CD38 is administered to an individual in combination with an interleukin-2 analogue (IL-2 analogue), wherein the CD38 antibody is isatuximab, and wherein the IL-2 analogue contains the unnatural amino acid JV6-((2-azidoethoxy)-carbonyl)-L-lysine (AzK), wherein AzK is PEGylated, wherein isatuximab is administered on days 1, 8, 15, and 22 of the first 28-day cycle and then administered on days 1 and 15 of the 28-day cycle for at least one additional cycle, in this case, isatuximab is administered intravenously at a dose of 10 mg / kg or administered subcutaneously at a dose of 1400 mg, wherein the IL-2 analogue is administered to the individual once every two weeks or once every three weeks at a dose of 16 mcg / kg, 24 mcg / kg or 32 mcg / kg, and wherein the individual has received one or more lines of therapy for the treatment of multiple myeloma prior to receiving the first cycle of treatment, wherein the one or more prior lines of therapy include an anti-CD38 antibody drug and an anti-BCMA antibody drug.

9. The use according to any one of claims 1-3, 5 or 8, wherein the individual is additionally administered natural killer (NK) cells characterized by reduced or knocked out expression of CD38 (NK-CD38KO cells).

10. The use according to claim 9, wherein the NK cells were isolated from a sample obtained from a human.

11. A method of treating a human subject with multiple myeloma, comprising administering to the individual an anti-CD38 antibody and an interleukin-2 analog (IL-2 analog), wherein the anti-CD38 antibody is administered on days 1, 8, 15, and 22 of the first 28-day cycle and then administered on days 1 and 15 of the 28-day cycle for at least one additional cycle, and administering to the individual an IL-2 analogue, wherein the IL-2 analogue is administered once every two weeks or once every three weeks.

12. The method according to claim 11, wherein the antibody to CD38 is isatuximab and is administered intravenously at a dose of 10 mg / kg.

13. The method according to claim 11, wherein the antibody to CD-38 is isatuximab and is administered subcutaneously at a dose of 1400 mg.

14. The method according to any one of claims 11-13, wherein the IL-2 analogue comprises the unnatural amino acid JV6-((2-azidoethoxy)-carbonyl)-L-lysine (AzK), and wherein AzK is PEGylated.

15. The method according to claim 14, wherein the IL-2 analogue is administered at a dose of 16 mcg / kg, 24 mcg / kg or 32 mcg / kg.

16. The method according to any one of claims 11-13 or 15, wherein the anti-CD38 antibody is administered on days 1 and 15 of a 28-day cycle for at least 11 cycles, followed by administration of the anti-CD38 antibody on day 1 of a 28-day cycle for one or more additional cycles.

17. A method of treating a human subject with multiple myeloma, comprising administration to an individual of an antibody to CD38 and an interleukin-2 analogue (IL-2 analogue), wherein the CD38 antibody is isatuximab, and wherein the IL-2 analogue contains the unnatural amino acid N6-((2-azidoethoxy)-carbonyl)-L-lysine (AzK), wherein AzK is PEGylated, wherein isatuximab is administered on days 1, 8, 15, and 22 of the first 28-day cycle and then administered on days 1 and 15 of the 28-day cycle for at least one additional cycle, and in this case, isatuximab is administered intravenously at a dose of 10 mg / kg or administered subcutaneously at a dose of 1400 mg, wherein the IL-2 analogue is administered to the individual once every two weeks or once every three weeks at a dose of 16 mcg / kg, 24 mcg / kg or 32 mcg / kg, and wherein the individual has received one or more lines of therapy for the treatment of multiple myeloma prior to receiving the first cycle of treatment, wherein the one or more prior lines of therapy include an anti-CD38 antibody drug and an anti-BCMA antibody drug.

18. The method according to any one of claims 11-13, 15 or 17, wherein the individual is additionally administered natural killer (NK) cells characterized by reduced or knocked out expression of CD38 (NK-CD38KO cells).

19. The method of claim 18, wherein the NK cells were isolated from a sample obtained from a human.