Methods of treating multiple myeloma with immunomodulatory compounds in combination with antibodies
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.
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, wherein the patient has received induction therapy with a compound having the formula:
or a pharmaceutically acceptable salt, solvate or stereoisomer thereof before receiving the stem cell transplantation; and
b. wherein if the patient is MRD positive, administering to the patient about 1 to about 50 mg per day of the compound
or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, in combination with a therapeutically effective amount of an anti-CS1 antibody.
2. The method of claim 1 , wherein the patient has received induction therapy with a combination of the compound and a proteasome inhibitor 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 in a 28 day cycle.
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
and is not a pharmaceutically acceptable salt, solvate or stereoisomer thereof.
26. The method of claim 1 , wherein the compound is a pharmaceutically acceptable salt of
27. The method of claim 1 , wherein the compound is a pharmaceutically acceptable solvate of
28. The method of claim 2 , 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 22 , wherein the patient is further administered with dexamethasone.
35. The method of claim 34 , wherein the dexamethasone is administered daily or on weeks when the anti-CS1 antibody is not administered in the cycle.