Use of inhibitors of brutons 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.

What is claimed is: 
     
         1 . A method for treating marginal zone lymphoma (MZL) in an individual comprising administering to the individual a dose of 560 mg of an inhibitor of Bruton's tyrosine kinase (Btk), wherein the inhibitor of Btk has the structure: 
       
         
           
           
               
               
           
         
       
     
     
         2 . The method of  claim 1 , wherein the individual is treatment naïve for marginal zone lymphoma (MZL). 
     
     
         3 . The method of  claim 1 , comprising the use of an additional cancer treatment with the compound. 
     
     
         4 . The method of  claim 3 , wherein the additional cancer treatment is rituximab. 
     
     
         5 . The method of  claim 1 , wherein the Btk inhibitor is administered once per day. 
     
     
         6 . The method of  claim 1 , wherein the Btk inhibitor is administered in the form of a solid oral dosage form. 
     
     
         7 . The method of  claim 6 , wherein the solid oral dosage form is a capsule. 
     
     
         8 . The method of  claim 6 , wherein the solid oral dosage form is a tablet. 
     
     
         9 . The method of  claim 1 , wherein said administering results in an AUC (0-24) of greater than about 100 ng*h/ml. 
     
     
         10 . The method of  claim 1 , wherein said administering results in greater than 90% of the Btk active sites in the peripheral blood mononuclear cells of the individual being occupied by the inhibitor twenty-four hours following said administering. 
     
     
         11 . The method of  claim 1 , wherein the Btk inhibitor is administered on a continuous once-daily regimen until progression of the marginal zone lymphoma or unacceptable toxicity. 
     
     
         12 . The method of  claim 11 , wherein the once-daily regimen is continued for at least 6 months. 
     
     
         13 . The method of  claim 1 , wherein following the administration of the Btk inhibitor, the individual achieves a stable disease, a partial response, or a complete response. 
     
     
         14 . The method of  claim 1 , wherein following the administration of the Btk inhibitor, the individual achieves a partial response or a complete response. 
     
     
         15 . The method of  claim 1 , wherein following the administration of the Btk inhibitor, the individual achieves a complete response. 
     
     
         16 . The method of  claim 13 , wherein the individual is treatment naïve for marginal zone lymphoma (MZL). 
     
     
         17 . The method of  claim 1 , wherein, following administration of the inhibitor, the individual does not experience a progressive disease. 
     
     
         18 . The method of  claim 17 , wherein the individual achieves a complete response. 
     
     
         19 . The method of  claim 9 , wherein said administering results in greater than 90% of the Btk active sites in the peripheral blood mononuclear cells of the individual being occupied by the inhibitor twenty-four hours following said administering, and the Btk inhibitor is administered on a continuous once-daily regimen. 
     
     
         20 . The method of  claim 19 , wherein, following administration of the inhibitor, the individual does not experience a progressive disease.