Patent Application

App. No. 16/227,893

Abstract

Claims (35)

1 . A combination comprising panobinostat, or a pharmaceutically acceptable salt thereof, and bortezomib for use in a method of treatment of multiple myeloma in a patient, where in the method comprises;

assaying a blood sample from the patient;

determining if the patient has no hepatic impairment or has mild, moderate or severe hepatic impairment; and

administering to the patient:

a starting dosage of 20 mg panobinostat if the patient has no or mild hepatic impairment;

a starting dosage of 10 mg of panobinostat if the patient has moderate hepatic impairment; and

not administering panobinostat if the patient has severe hepatic impairment;

wherein mild hepatic impairment is bilirubin≤1×the upper limit of the normal range (“ULN”) and aspartate aminotransferase (“AST”)>1×ULN, or bilirubin>1.0-≤1.5×ULN and any amount of AST above ULN is present;

wherein moderate hepatic impairment is bilirubin>1.5×-≤3.0×ULN and any amount of AST above ULN is present;

wherein severe hepatic impairment is bilirubin>3.0×ULN and any amount of AST above ULN is present; and

wherein panobinostat, or a pharmaceutically acceptable salt thereof (e.g. the lactate or the anhydrous lactate salt thereof) is in the form of an oral dosage form.

2 . A combination according to claim 1 for use according to claim 1 , wherein the method further comprises administering to the patient an effective dosage of dexamethasone.

3 . A combination according to claim 1 for use according to claim 1 or 2 , wherein the multiple myeloma is resistant or refractory to prior treatments.

4 . A combination according to claim 1 for use according to claim 1 or 2 or 3 , wherein the dosage of bortezomib is 1.3 mg/m 2 administered as an injection.

5 . A combination according to claim 1 for use according to claim 1 or 2 or 3 wherein the bortezomib is administered at a dosage of 0.7 mg/m 2 and wherein the patient has mild hepatic impairment.

6 . A combination according to claim 1 for use according to claim 1 or 2 or 3 or 4 or 5 , wherein the prior treatments have been treatment with bortezomib or an immunomodulatory agent.

7 . A combination according to claim 1 for use according to claim 6 , wherein the prior treatments have included both bortezomib and an immunomodulatory agent.

8 . A combination according to claim 1 for use according to claim 6 , wherein the prior treatments were a chemotherapeutic agent.

9 . A method of treating a human patient having multiple myeloma comprising:

assaying a blood sample from the patient;

determining if the patient has no hepatic impairment or has mild, moderate or severe hepatic impairment; and

administering to the patient:

a starting dosage of 20 mg of panobinostat if the patient has no hepatic impairment;

a starting dosage of 15 mg of panobinostat if the patient has mild hepatic impairment;

a starting dosage of 10 mg of panobinostat if the patient has moderate hepatic impairment; and

not administering panobinostat if the patient has severe hepatic impairment

wherein mild hepatic impairment is bilirubin<1×the upper limit of the normal range (“ULN”) and aspartate aminotransferase (“AST”)>1×ULN, or bilirubin>1.0 to 1.5×ULN and any amount of AST above ULN is present);

wherein moderate hepatic impairment is bilirubin>1.5× to 3.0×ULN and any amount of AST above ULN is present;

wherein severe hepatic is bilirubin>3.0×ULN and any amount of AST above ULN is present; and

wherein the term panobinostat is the molecule itself or a pharmaceutically acceptable salt thereof.

10 . The method of claim 6 , wherein the patient is also administered an effective dosage of dexamethasone.

11 . The method of claim 6 , wherein the multiple myeloma is resistant or refractory to prior treatments.

12 . The method of claim 9 , wherein the prior treatments have been treatment with bortezomib or an immunomodulatory agent.

13 . The method of claim 12 , wherein the prior treatments have included both bortezomib and an immunomodulatory agent.

14 . The method of claim 9 , wherein the prior treatments included or consisted of treatment with a chemotherapeutic agent.

Assignments (11)