Use of inhibitors of bruton's tyrosine kinase (btk)

Abstract

Disclosed herein are methods for treating a cancer comprising: a. administering a Btk inhibitor to a subject sufficient to result in an increase or appearance in the blood of a subpopulation of lymphocytes defined by immunophenotyping; b. determining the expression profile of one or more biomarkers from one or more subpopulation of lymphocytes; and c. administering a second agent based on the determined expression profile.

1 .- 129 . (canceled) 
     
     
         130 . A method for treating relapsed or refractory lymphoma in an individual comprising administering to the individual in need thereof an irreversible inhibitor of Bruton's tyrosine kinase (Btk), having the structure: 
       
         
           
           
               
               
           
         
         wherein the individual is one having received at least two anticancer agents prior to administration of the irreversible Btk inhibitor. 
       
     
     
         131 . The method of  claim 130 , wherein the relapsed or refractory lymphoma is a relapsed or refractory lymphoma Non-Hodgkin's lymphoma (NHL). 
     
     
         132 . The method of  claim 131 , wherein the relapsed or refractory Non-Hodgkin's lymphoma (NHL) is a relapsed or refractory mantle cell lymphoma, a relapsed or refractory chronic lymphocytic leukemia, a relapsed or refractory small lymphocytic lymphoma, or a relapsed or refractory follicular lymphoma. 
     
     
         133 . The method of  claim 130 , wherein at least at least one of the two anticancer agents is an antibody, a nucleoside analog, or an alkylating agent. 
     
     
         134 . The method of  claim 133 , wherein the antibody is an anti-CD20 or anti-CD52 antibody. 
     
     
         135 . The method of  claim 134 , wherein the anti-CD20 antibody is rituximab or ofatumumab. 
     
     
         136 . The method of  claim 134 , wherein the anti-CD52 antibody is alemtuzumab. 
     
     
         137 . The method of  claim 130 , wherein at least at least one of the two anticancer agents is bortezomib. 
     
     
         138 . The method of  claim 130 , wherein the individual is one having received three or four anticancer agents prior to administration of the Btk inhibitor. 
     
     
         139 . The method of  claim 130 , wherein the individual is resistant to treatment with an anti-CD20 antibody. 
     
     
         140 . The method of  claim 139 , wherein the individual is resistant to treatment with rituximab or ofatumumab. 
     
     
         141 . The method of  claim 130 , wherein the relapsed or refractory lymphoma is a relapsed or refractory follicular lymphoma, and the individual is one having received rituximab or ofatumumab prior to administration of the Btk inhibitor. 
     
     
         142 . The method of  claim 130 , wherein the relapsed or refractory lymphoma is a relapsed or refractory mantle cell lymphoma, and the individual is one having received rituximab or ofatumumab prior to administration of the Btk inhibitor. 
     
     
         143 . The method of  claim 130 , wherein the relapsed or refractory lymphoma is a relapsed or refractory mantle cell lymphoma, and the individual is one having received bortezomib prior to administration of the Btk inhibitor. 
     
     
         144 . The method of  claim 130 , wherein the relapsed or refractory lymphoma is a relapsed or refractory chronic lymphocytic leukemia or relapsed or refractory small lymphocytic lymphoma, and the individual is one having received rituximab, ofatumumab, or alemtuzumab prior to administration of the Btk inhibitor. 
     
     
         145 . The method of  claim 130 , further comprising administering a second cancer treatment regimen with the inhibitor of Btk. 
     
     
         146 . The method of  claim 145 , wherein the second cancer treatment regimen comprises bendamustine, bortezomib, CAL-101, chlorambucil, cyclophosphamide, dexamethasone, docetaxel, doxorubicin, endostatineverolimus, etoposide, fludarabine, fostamatinib, hydroxydaunorubicin, ibritumomab, ifosphamide, lenalidomide, mesalazine, ofatumumab, paclitaxel, pentostatin, prednisone, rituximab, temsirolimus, thalidomide, tositumomab, vincristine, or a combination thereof. 
     
     
         147 . The method of  claim 130 , wherein the Btk inhibitor is administered orally. 
     
     
         148 . The method of  claim 130 , wherein the Btk inhibitor is in the form of a solid oral dosage form. 
     
     
         149 . The method of  claim 130 , wherein the amount of the Btk inhibitor administered is from about 300 mg/day to about 1000 mg/day. 
     
     
         150 . The method of  claim 130 , wherein the amount of the Btk inhibitor administered is about 420 mg/day, about 560 mg/day, or about 840 mg/day.