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 chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in an individual in need thereof, wherein the individual is treatment-naïve for CLL/SLL, comprising:
administering to the individual once per day about 420 mg of an oral dose of a compound having the structure:
2. The method of claim 1 , wherein the individual has high risk CLL.
3. The method of claim 1 , wherein the individual has nucleic acid deletion in chromosome 17.
4. The method of claim 3 , wherein the deletion is in 17p.
5. The method of claim 4 , wherein the deletion is in 17p13.
6. The method of claim 1 , wherein the individual has nucleic acid deletion in chromosome 11.
7. The method of claim 6 , wherein the deletion is in 11q.
8. The method of claim 7 , wherein the deletion is in 11q22.
9. The method of claim 1 , further comprising administering to the individual an additional cancer treatment regimen.
10. The method of claim 9 , wherein the additional cancer treatment regimen comprises bendamustine, bortezomib, CAL-101, chlorambucil, cyclophosphamide, dexamethasone, docetaxel, doxorubicin, endostatin, everolimus, etoposide, fludarabine, fostamatinib, hydroxydaunorubicin, ibritumomab, ifosphamide, lenalidomide, mesalazine, ofatumumab, paclitaxel, pentostatin, prednisone, rituximab, temsirolimus, thalidomide, tositumomab, vincristine, or a combination thereof.
11. The method of claim 1 , further comprising administering to the individual rituximab.
12. The method of claim 1 , further comprising administering to the individual bendamustine.
13. The method of claim 1 , further comprising administering to the individual rituximab and bendamustine.
14. The method of claim 1 , further comprising administering to the individual rituximab, fludarabine, and cyclophosphamide.
15. The method of claim 1 , further comprising administering to the individual rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.
16. The method of claim 1 , wherein the oral dose is a solid oral dosage form.
17. The method of claim 1 , wherein the oral dose is a capsule.
18. The method of claim 1 , wherein the individual is ≧65 years of age.
19. The method of claim 1 , wherein the method is a method for treating CLL in an individual who is treatment-naïve for CLL.
20. The method of claim 1 , wherein the method is a method for treating SLL in an individual who is treatment-nave for SLL.
21. The method of claim 1 , wherein, following administration of the compound, the individual achieves a stable disease, a partial response, or a complete response.
22. The method of claim 1 , wherein, following administration of the compound, the individual achieves a partial response or a complete response.
23. The method of claim 1 , wherein, following administration of the compound, the individual achieves a complete response.
24. The method of claim 1 , wherein, following administration of the compound, the individual does not experience a progressive disease.
25. A method for treating chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in an individual in need thereof, wherein the individual is treatment-nave for CLL/SLL, comprising:
administering to the individual once per day about 420 mg of an oral dose of a compound having the structure:
wherein the individual has a 17p deletion.
26. The method of claim 25 , wherein the method is a method for treating CLL in an individual who is treatment-naïve for CLL.
27. The method of claim 25 , wherein the method is a method for treating SLL in an individual who is treatment-naïve for SLL.
28. The method of claim 25 , wherein, following administration of the compound, the individual achieves a stable disease, a partial response, or a complete response.
29. The method of claim 25 , wherein, following administration of the compound, the individual achieves a partial response or a complete response.
30. The method of claim 25 , wherein, following administration of the compound, the individual achieves a complete response.
31. The method of claim 25 , wherein, following administration of the compound, the individual does not experience a progressive disease.