METHODS OF TREATING A DISEASE OR DISORDER ASSOCIATED WITH BRUTON'S TYROSINE KINASE
The present invention provides methods of treating, stabilizing or lessening the severity or progression of a disease or disorder associated with BTK.
1 . A method of treating, stabilizing or lessening the severity or progression of a B-cell non-Hodgkin lymphoma comprising administering to a patient in need thereof. Compound 1 (N-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide):
or a pharmaceutically acceptable salt thereof, and lenalidomide.
2 . The method according to claim 1 , wherein the B-cell non-Hodgkin lymphoma is indolent.
3 . The method according to claim 2 , wherein the indolent B-cell non-Hodgkin lymphoma is selected from follicular lymphoma and marginal zone lymphoma.
4 . The method according to claim 3 , wherein marginal zone lymphoma is selected from nodal marginal zone lymphoma, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue and splenic marginal zone lymphoma.
5 . The method according to claim 1 , wherein the B-cell non-Hodgkin lymphoma is aggressive.
6 . The method according to claim 5 , wherein the aggressive B-cell non-Hodgkin lymphoma is selected from diffuse large B-cell non-Hodgkin lymphoma and mantle cell lymphoma.
7 . The method according to claim 1 , wherein Compound 1 is administered twice a day.
8 . The method according to claim 7 , wherein Compound 1 is in the form of a benzenesulfonic acid salt.
9 . The method according to claim 8 , wherein lenalidomide is administered once a day.
10 . The method of claim 9 , wherein each of Compound 1 and lenalidomide is administered as an oral dosage form.
11 . The method according to claim 10 , wherein each of Compound 1 and lenalidomide is administered for at least one 28-day cycle.
12 . The method according to claim 1 , wherein the patient has failed at least one prior therapy.
13 . The method according to claim 8 , wherein Compound 1 is administered in the form of a composition comprising from about 10% to about 50% N-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide besylate.
14 . The method according to claim 13 , wherein the composition comprises about 42% N-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide besylate.
15 . A method of preventing, treating, stabilizing or lessening the severity or progression of a B-cell non-Hodgkin lymphoma, the method comprising administering to a patient in need thereof a therapeutically effective amount of Compound 1, or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of lenalidomide, wherein the therapeutically effective amount of Compound 1 is about 750 mg to about 1000 mg per day.
16 . The method according to claim 15 , wherein the therapeutically effective amount of Compound 1 is about 375 mg BID.
17 . The method according to claim 15 , wherein the therapeutically effective amount Compound 1 is about 500 mg BID.
18 . The method according to any of claim 15 , wherein lenalidomide is administered once a day (QD).
19 . The method according to claim 18 , wherein the therapeutically effective amount of lenalidomide is about 15 mg.
20 . The method according to claim 18 , wherein the therapeutically effective amount of lenalidomide is about 20 mg.
21 . The method according to claim 18 , wherein the therapeutically effective amount of lenalidomide is about 25 mg.
22 . A system for treating, stabilizing or lessening the severity of a B-cell non-Hodgkin lymphoma, the system comprising Compound 1, or a pharmaceutically acceptable salt thereof, and lenalidomide.