Methods of treating B-cell proliferative disorder

1. A method of treating or delaying progression of a B-cell proliferative disorder in a patient receiving a moderate CYP3A inducer, the method comprising

concomitantly administering to the patient zanubrutinib, or a pharmaceutically acceptable salt thereof, at a total daily dose of about 640 mg, and the moderate CYP3A inducer,

wherein the B-cell proliferative disorder is chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), or follicular lymphoma (FL).

2. The method of claim 1 , wherein zanubrutinib is administered at a dose of about 320 mg twice a day.

3. The method of claim 1 , wherein the B-cell proliferative disorder is chronic lymphocytic leukemia (CLL).

4. The method of claim 1 , wherein the B-cell proliferative disorder is small lymphocytic lymphoma (SLL).

5. The method of claim 1 , wherein the B-cell proliferative disorder is Waldenström macroglobulinemia (WM).

6. The method of claim 1 , wherein the B-cell proliferative disorder is mantle cell lymphoma (MCL).

7. The method of claim 1 , wherein the B-cell proliferative disorder is marginal zone lymphoma (MZL).

8. The method of claim 1 , wherein the moderate CYP3A inducer is rifabutin, bosentan, efavirenz, etravirine, modafinil, phenobarbital or nafcillin.

9. The method of claim 1 , wherein the administration prolongs the progression-free survival (PFS) time of the patient as compared to the PFS time of a comparable patient orally administered with ibrutinib at a dose of 420 mg once daily.

10. The method of claim 1 , wherein the administration causes lower rate of atrial fibrillation or flutter as compared to the rate of atrial fibrillation or flutter of a comparable patient orally administered with ibrutinib at a dose of 420 mg once daily.

11. A method of treating or delaying progression of a B-cell proliferative disorder in a patient, the method comprising

determining whether the patient is being treated with a moderate CYP3A inducer; and

if the patient is being treated with a moderate CYP3A inducer, concomitantly administering to the patient zanubrutinib, or a pharmaceutically acceptable salt thereof, at a total daily dose of about 640 mg; and the moderate CYP3A inducer,

wherein the B-cell proliferative disorder is chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), or follicular lymphoma (FL).

12. The method of claim 11 , wherein zanubrutinib is administered at a dose of about 320 mg twice a day.

13. The method of claim 11 , wherein the B-cell proliferative disorder is chronic lymphocytic leukemia (CLL).

14. The method of claim 11 , wherein the B-cell proliferative disorder is small lymphocytic lymphoma (SLL).

15. The method of claim 11 , wherein the B-cell proliferative disorder is Waldenström macroglobulinemia (WM).

16. The method of claim 11 , wherein the B-cell proliferative disorder is mantle cell lymphoma (MCL).

17. The method of claim 11 , wherein the B-cell proliferative disorder is marginal zone lymphoma (MZL).

18. The method of claim 11 , wherein the moderate CYP3A inducer is rifabutin, bosentan, efavirenz, etravirine, modafinil, phenobarbital or nafcillin.

19. The method of claim 11 , wherein the administration prolongs the progression-free survival (PFS) time of the patient as compared to the PFS time of a comparable patient orally administered with ibrutinib at a dose of 420 mg once daily.

20. The method of claim 11 , wherein the administration causes lower rate of atrial fibrillation or flutter as compared to the rate of atrial fibrillation or flutter of a comparable patient orally administered with ibrutinib at a dose of 420 mg once daily.

21. A method of treating or delaying progression of a B-cell proliferative disorder in a patient receiving a moderate CYP3A inducer, the method comprising

assessing the patient as to whether administration of the moderate CYP3A inducer can be avoided; and

if the administration of the moderate CYP3A inducer cannot be avoided, concomitantly administering to the patient zanubrutinib, or a pharmaceutically acceptable salt thereof, at a total daily dose of about 640 mg, and the moderate CYP3A inducer,

wherein the B-cell proliferative disorder is chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), or follicular lymphoma (FL).

22. The method of claim 21 , wherein zanubrutinib is administered at a dose of about 320 mg twice a day.

23. The method of claim 21 , wherein the B-cell proliferative disorder is chronic lymphocytic leukemia (CLL).

24. The method of claim 21 , wherein the B-cell proliferative disorder is small lymphocytic lymphoma (SLL).

25. The method of claim 21 , wherein the B-cell proliferative disorder is Waldenström macroglobulinemia (WM).

26. The method of claim 21 , wherein the B-cell proliferative disorder is mantle cell lymphoma (MCL).

27. The method of claim 21 , wherein the B-cell proliferative disorder is marginal zone lymphoma (MZL).

28. The method of claim 21 , wherein the moderate CYP3A inducer is rifabutin, bosentan, efavirenz, etravirine, modafinil, phenobarbital or nafcillin.

29. The method of claim 21 , wherein the administration prolongs the progression-free survival (PFS) time of the patient as compared to the PFS time of a comparable patient orally administered with ibrutinib at a dose of 420 mg once daily.

30. The method of claim 21 , wherein the administration causes lower rate of atrial fibrillation or flutter as compared to the rate of atrial fibrillation or flutter of a comparable patient orally administered with ibrutinib at a dose of 420 mg once daily.