METHODS OF TREATING MULTIPLE MYELOMA WITH IMMUNOMODULATORY COMPOUNDS IN COMBINATION WITH ANTIBODIES

• US 20160051530A1
• Filed: 08/20/2015
• Published: 02/25/2016
• Est. Priority Date: 08/22/2014
• Status: Active Grant

• Current Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Original Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Inventors: THAKURTA, Anjan, HUSSEIN, Mohamed, JACQUES, Christian
• Granted Patent: US 10,034,872 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55 characterised by the host/recipient, e.g. newborn with maternal antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61K 38/07 Tetrapeptides
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/3061 Blood cells
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

Methods of treating, preventing and/or managing multiple myeloma are disclosed. Specific methods encompass the administration of an immunomodulatory compound, e.g., lenalidomide or pomalidomide with an anti-CS1 antibody, e.g., elotuzumab in patients who have received autologous stem cell transplantation.

Claims

1. A method of treating multiple myeloma in a patient having multiple myeloma and having received stem cell transplantation, which comprises:

a. determining the minimal residual disease (MRD) status of the patient following the stem cell transplantation; and

b. if the patient is MRD positive, administering to the patient about 1 to about 50 mg per day of a compound having the formula;

2. The method of claim 1, wherein the patient has received induction therapy with the compound, a proteasome inhibitor, or a combination thereof prior to the stem cell transplantation.

3. The method of claim 1, wherein the multiple myeloma is relapsed, refractory, or relapsed and refractory multiple myeloma.

4. The method of claim 1, wherein the method comprises cyclic administration of the compound.

5. The method of claim 4, wherein the compound is administered for 21 days followed by seven days of rest in a 28 day cycle.

6. The method of claim 1, wherein the compound is administered in an amount of about 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg or 25 mg per day.

7. The method of claim 6, wherein the compound is administered in an amount of about 25 mg per day.

8. The method of claim 6, wherein the compound is administered in an amount of about 10 mg per day.

9. The method of claim 6, wherein the compound is administered in an amount of about 5 mg per day.

10. The method of claim 6, wherein the compound is administered in a capsule in an amount of about 25 mg.

11. The method of claim 1, wherein the compound is administered orally.

12. The method of claim 11, wherein the compound is administered in the form of a capsule or tablet.

13. The method of claim 12, wherein the capsule comprises the compound, lactose anhydrous, microcrystalline cellulose, croscarmellose sodium and magnesium stearate.

14. The method of claim 1, wherein the compound is administered in a capsule in an amount of 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg or 25 mg.

15. The method of claim 14, wherein the compound is administered in a capsule in an amount of about 10 mg.

16. The method of claim 14, wherein the compound is administered in a capsule in an amount of about 5 mg.

17. The method of claim 14, wherein the compound is administered in a capsule in an amount of about 2.5 mg.

18. The method of claim 1, wherein the anti-CS1 antibody is a monoclonal antibody.

19. The method of claim 18, wherein the anti-CS1 antibody is elotuzumab.

20. The method of claim 18, wherein the antibody is administered intravenously in an amount of from about 1 to about 1000 mg weekly or every other week.

21. The method of claim 18, wherein the antibody is administered in an amount of about 10 mg/kg.

22. The method of claim 18, wherein the antibody is administered weekly or every other week.

23. The method of claim 18, wherein the antibody is administered on days 1, 8, 15 and 22 in a 28 day cycle.

24. The method of claim 18, wherein the antibody is administered on days 1 and 15 in a 28 day cycle.

25. The method of claim 1, wherein the compound is

26. The method of claim 1, wherein the compound is a pharmaceutically acceptable salt.

27. The method of claim 1, wherein the compound is a pharmaceutically acceptable solvate.

28. The method of claim 1, wherein the proteasome inhibitor is bortezomib or carfilzomib.

29. The method of claim 28, wherein the patient has received induction therapy with lenalidomide in combination with bortezomib or carfilzomib.

30. The method of claim 28, wherein the patient has received induction therapy with lenalidomide in combination with bortezomib or carfilzomib, and dexamethasone.

31. The method of claim 1, wherein the stem cell transplantation is autologous stem cell transplantation.

32. The method of claim 1, wherein the stem cell transplantation is hematopoietic stem cell transplantation.

33. The method of claim 1, wherein the stem cell transplantation is peripheral blood stem cell transplantation.

34. The method of claim 1, wherein the patient is minimal residual disease (MRD) positive following the stem cell transplatation.

35. The method of claim 1, wherein the patient is minimal residual disease (MRD) negative following the stem cell transplatation.

36-51. -51. (canceled)