Tec family kinase inhibitor adjuvant therapy

Abstract

Described herein are methods and compositions comprising a covalent TEC family kinase inhibitor for use in adjuvant therapy, including adjuvant cancer therapy, vaccination and treatment of immune disorders and pathogenic infections.

1 - 34 . (canceled) 
     
     
         35 . A method of treating a myeloma or lymphoma in a subject in need thereof comprising co-administering:
 a. a first amount of ibrutinib; and   b. a second amount of bortezomib,   
       wherein, together, the first amount of ibrutinib and the second amount of bortezomib are therapeutically effective. 
     
     
         36 . The method of  claim 35 , wherein the myeloma or lymphoma is a relapsed or refractory myeloma or lymphoma. 
     
     
         37 . The method of  claim 35 , wherein the lymphoma is non-Hodgkin's lymphoma. 
     
     
         38 . The method of  claim 35 , wherein the myeloma is multiple myeloma. 
     
     
         39 . The method of  claim 35 , wherein the lymphoma is mantle cell lymphoma. 
     
     
         40 . The method of  claim 35 , wherein the myeloma is relapsed or refractory multiple myeloma. 
     
     
         41 . The method of  claim 35 , wherein the lymphoma is relapsed or refractory mantle cell lymphoma. 
     
     
         42 . The method of  claim 35 , wherein, following co-administration of ibrutinib and bortezomib, the subject achieves a longer disease free survival (DFS) than a control subject who was administered bortezomib alone. 
     
     
         43 . The method of  claim 35 , wherein, following co-administration of ibrutinib and bortezomib, the subject achieves a longer overall survival (OS) than a control subject who was administered bortezomib alone. 
     
     
         44 . The method of  claim 35 , wherein, following co-administration of ibrutinib and bortezomib, the subject does not experience a relapse of the myeloma or lymphoma for about 6 months, about 1 year, about 2 years, about 3 years, about 4 years, about 5 years, about 6 years, about 7 years, about 8 years, about 9 years, or about 10 years. 
     
     
         45 . The method of  claim 35 , wherein, following co-administration of ibrutinib and bortezomib, the subject experiences a reduced risk of relapsed or refractory myeloma or lymphoma as compared to a control subject who was administered bortezomib alone. 
     
     
         46 . The method of  claim 42 , wherein the risk of relapsed or refractory myeloma or lymphoma is reduced by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 90% as compared to the control subject. 
     
     
         47 . The method of  claim 35 , wherein the subject experiences a decreased risk of developing a secondary tumor as compared to a control subject who was administered bortezomib alone. 
     
     
         48 . The method of  claim 35 , wherein, prior to co-administration of ibrutinib and bortezomib, the subject exhibits abnormal B-cell function, abnormal B-cell size, abnormal B-cell shape, abnormal B-cell count, fatigue, fever, night sweats, frequent infection, enlarged lymph nodes, paleness, anemia, loss of appetite, weight loss, bone or joint pain, headaches, or petechie. 
     
     
         49 . The method of  claim 35 , wherein the first amount of ibrutinib is about 300 mg per day to about 600 mg per day. 
     
     
         50 . The method of  claim 35 , wherein the first amount of ibrutinib is about 420 mg per day. 
     
     
         51 . The method of  claim 35 , wherein ibrutinib is administered once per day. 
     
     
         52 . The method of  claim 35 , wherein ibrutinib is administered orally. 
     
     
         53 . The method of  claim 35 , wherein ibrutinib is administered orally once per day. 
     
     
         54 . The method of  claim 35 , wherein about 420 mg of ibrutinib is administered orally once per day. 
     
     
         55 . The method of  claim 35 , wherein bortezomib is administered intravenously. 
     
     
         56 . A method of treating a myeloma or lymphoma in a subject in need thereof comprising co-administering:
 a. a first amount of ibrutinib;   b. a second amount of bortezomib; and   c. a third amount of a corticosteroid,   
       wherein, together, the first amount of ibrutinib, the second amount of bortezomib, and the third amount of the corticosteroid are therapeutically effective. 
     
     
         57 . The method of  claim 56 , wherein the corticosteroid is dexamethasone. 
     
     
         58 . The method of  claim 57 , wherein the myeloma or lymphoma is a relapsed or refractory myeloma or lymphoma. 
     
     
         59 . The method of  claim 57 , wherein the lymphoma is non-Hodgkin's lymphoma. 
     
     
         60 . The method of  claim 57 , wherein the myeloma is multiple myeloma. 
     
     
         61 . The method of  claim 57 , wherein the lymphoma is mantle cell lymphoma. 
     
     
         62 . The method of  claim 57 , wherein the myeloma is relapsed or refractory multiple myeloma. 
     
     
         63 . The method of  claim 57 , wherein the lymphoma is relapsed or refractory mantle cell lymphoma. 
     
     
         64 . The method of  claim 57 , wherein, following co-administration of ibrutinib, bortezomib, and dexamethasone, the subject achieves a longer disease free survival (DFS) than a control subject who was co-administered bortezomib and dexamethasone. 
     
     
         65 . The method of  claim 57 , wherein, following co-administration of ibrutinib, bortezomib, and dexamethasone, the subject achieves a longer overall survival (OS) than a control subject who was co-administered bortezomib and dexamethasone. 
     
     
         66 . The method of  claim 57 , wherein, following co-administration of ibrutinib, bortezomib, and dexamethasone, the subject does not experience a relapse of the myeloma for about 6 months, about 1 year, about 2 years, about 3 years, about 4 years, about 5 years, about 6 years, about 7 years, about 8 years, about 9 years, or about 10 years. 
     
     
         67 . The method of  claim 57 , wherein, following co-administration of ibrutinib, bortezomib, and dexamethasone, the subject experiences a reduced risk of relapsed or refractory myeloma or lymphoma as compared to a control subject who was co-administered bortezomib and dexamethasone. 
     
     
         68 . The method of  claim 67 , wherein the risk of relapsed or refractory myeloma is reduced by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 90% as compared to the control subject. 
     
     
         69 . The method of  claim 57 , wherein the subject experiences a decreased risk of developing a secondary tumor as compared to a control subject who was co-administered bortezomib and dexamethasone. 
     
     
         70 . The method of  claim 57 , wherein, prior to co-administration of ibrutinib, bortezomib, and dexamethasone, the subject exhibits abnormal B-cell function, abnormal B-cell size, abnormal B-cell shape, abnormal B-cell count, fatigue, fever, night sweats, frequent infection, enlarged lymph nodes, paleness, anemia, loss of appetite, weight loss, bone or joint pain, headaches, or petechie. 
     
     
         71 . The method of  claim 57 , wherein the first amount of ibrutinib is about 300 mg per day to about 600 mg per day. 
     
     
         72 . The method of  claim 57 , wherein the first amount of ibrutinib is about 420 mg per day. 
     
     
         73 . The method of  claim 57 , wherein ibrutinib is administered once per day. 
     
     
         74 . The method of  claim 57 , wherein ibrutinib is administered orally. 
     
     
         75 . The method of  claim 57 , wherein ibrutinib is administered orally once per day. 
     
     
         76 . The method of  claim 57 , wherein about 420 mg of ibrutinib is administered orally once per day. 
     
     
         77 . The method of  claim 57 , wherein bortezomib is administered intravenously. 
     
     
         78 . The method of  claim 57 , wherein dexamethasone is administered orally. 
     
     
         79 . A method of treating a myeloma or lymphoma in a subject in need thereof comprising co-administering:
 a. a first amount of ibrutinib, wherein the first amount is 300 mg to 600 mg; and   b. a second amount of bortezomib,   
       wherein ibrutinib is administered orally and bortezomib is administered intravenously; and wherein, together, the first amount of ibrutinib and the second amount of bortezomib are therapeutically effective. 
     
     
         80 . The method of  claim 79 , wherein ibrutinib is administered once per day. 
     
     
         81 . The method of  claim 79 , wherein the myeloma or lymphoma is a relapsed or refractory myeloma or lymphoma. 
     
     
         82 . The method of  claim 79 , wherein the lymphoma is non-Hodgkin's lymphoma. 
     
     
         83 . The method of  claim 79 , wherein the myeloma is multiple myeloma. 
     
     
         84 . The method of  claim 79 , wherein the lymphoma is mantle cell lymphoma. 
     
     
         85 . The method of  claim 79 , wherein the myeloma is relapsed or refractory multiple myeloma. 
     
     
         86 . The method of  claim 79 , wherein the lymphoma is relapsed or refractory mantle cell lymphoma. 
     
     
         87 . The method of  claim 79 , wherein the treatment further comprises co-administering:
 c. a third amount of dexamethasone,   
       wherein, together, the first amount of ibrutinib, the second amount of bortezomib, and the third amount of dexamethasone are therapeutically effective.