Use of inhibitors of bruton's tyrosine kinase (BTK)
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. A method for treating mantle cell lymphoma in an individual who has already received at least one prior therapy for mantle cell lymphoma comprising orally administering to the individual a dose of 560 mg of an inhibitor of Bruton's tyrosine kinase (Btk) on a continuous once-daily regimen until progression of the mantle cell lymphoma or unacceptable toxicity; and
lymphocytosis is not considered progression of the mantle cell lymphoma,
wherein the inhibitor of Btk has
the structure:
wherein the individual achieves a complete response.
2. The method of claim 1 , wherein said administering results in an AUC (0-24) of > about 100 ng*h/ml.
3. The method of claim 1 , wherein said administering results in >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.
4. The method of claim 1 , wherein the once-daily regimen is continued for at least 6 months.
5. A method for treating mantle cell lymphoma in an individual comprising orally administering to the individual a dose of 560 mg of an inhibitor of Bruton's tyrosine kinase (Btk) on a continuous once-daily regimen until progression of the mantle cell lymphoma or unacceptable toxicity; and
lymphocytosis is not considered progression of the mantle cell lymphoma,
wherein the inhibitor of Btk has
the structure:
wherein the individual achieves a complete response.
6. The method of claim 5 , wherein the individual is treatment nave.
7. The method of claim 5 , wherein said administering results in an AUC (0-24) of > about 100 ng*h/ml.
8. The method of claim 5 , wherein said administering results in >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.
9. The method of claim 5 , wherein the once-daily regimen is continued for at least 6 months.