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 pharmaceutical composition comprising about 140 mg of a Bruton's tyrosine kinase (BTK) inhibitor compound of Formula (D): 
       
         
           
           
               
               
           
         
         wherein 
         La is CH2, O, NH or S; 
         Ar is a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; 
         Y is an optionally substituted group selected from among alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; 
         Z is C(═O), OC(═O), NHC(═O), C(═S), S(═O)x, OS(═O)x, NHS(═O)x, where x is 1 or 2; 
         R7 and R8 are independently H; or 
         R7 and R8 taken together form a bond; 
         R6 is H, 
         and a pharmaceutically-acceptable excipient. 
       
     
     
         131 . The pharmaceutical composition of  claim 130 , wherein the dosage form is an oral dosage form. 
     
     
         132 . The pharmaceutical composition of  claim 130 , wherein the dosage form is a tablet, a pill, a powder, a capsule, a solid dispersion, a solid solution, a bioerodible dosage form, a controlled release formulation, a pulsatile release dosage form, a multiparticulate dosage form, a pellet, a granule, or an aerosol. 
     
     
         133 . The pharmaceutical composition of  claim 130 , wherein the dosage form is a capsule. 
     
     
         134 . The pharmaceutical composition of  claim 130 , wherein the dosage form is a tablet. 
     
     
         135 . The pharmaceutical composition of  claim 130 , wherein the dosage form is a pill. 
     
     
         136 . The pharmaceutical composition of  claim 130 , wherein the compound of Formula (D) is (R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one (ibrutinib). 
     
     
         137 . The pharmaceutical composition of  claim 136 , wherein the dosage form is an oral dosage form. 
     
     
         138 . The pharmaceutical composition of  claim 136 , wherein the dosage form is a tablet, a pill, a powder, a capsule, a solid dispersion, a solid solution, a bioerodible dosage form, a controlled release formulation, a pulsatile release dosage form, a multiparticulate dosage form, a pellet, a granule, or an aerosol. 
     
     
         139 . The pharmaceutical composition of  claim 136 , wherein the dosage form is a capsule. 
     
     
         140 . The pharmaceutical composition of  claim 136 , wherein the dosage form is a tablet. 
     
     
         141 . The pharmaceutical composition of  claim 136 , wherein the dosage form is a pill. 
     
     
         142 . A pharmaceutical composition comprising about 140 mg of (R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one (ibrutinib), and a pharmaceutically-acceptable excipient, formulated into a solid dosage form.