METHODS OF TREATING FLT3-MUTATED HEMATOLOGIC CANCERS
Methods to inhibit FLT3 activity in a subject or a cell with an FLT3 mutation are provided. Methods of treating a hematologic cancer, such as acute myeloid leukemia, in a subject identified as having an FLT3 mutation, are also provided.
1 . A method for treating a hematologic cancer in a subject having a genetic profile comprising an FLT3 mutation, the method comprising:
administering an effective amount of pacritinib, or a pharmaceutically acceptable salt or N-oxide thereof; and
wherein the FLT3 mutation comprises:
a) an internal tandem duplication (ITD) mutation;
b) a tyrosine kinase domain (TKD) mutation selected from D835H, D835V, and D835Y: or
c) an ITD mutation and a TKD mutation selected from ITD-D835H, ITD-D835V, ITD-D835Y, and JTD-F691L.
2 . The method of claim 1 , wherein the FLT3 mutation comprises an internal tandem duplication (JTD) mutation.
3 . The method of claim 1 , wherein the FLT3 mutation comprises a tyrosine kinase domain (TKD) mutation.
4 - 5 . (canceled)
6 . The method of claim 3 , wherein the TKD mutation is a FLT 835 mutation comprising D835Y.
7 - 8 . (canceled)
9 . The method of claim 1 , wherein the FLT3 mutation comprises an ITD mutation and a TKD mutation.
10 . The method of claim 9 , wherein the FLT3 mutation comprises ITD-F691L.
11 . The method of claim 9 , wherein the FLT3 mutation comprises ITD-835Y.
12 . (canceled)
13 . The method of claim 1 , wherein the pharmaceutically acceptable salt is a citrate salt.
14 . (canceled)
15 . The method of claim 1 , wherein the effective amount is between about 50 mg per day and about 500 mg per day.
16 . The method of claim 1 , wherein the method further comprises administering an effective amount of one or more further therapeutic agents.
17 . The method of claim 16 , wherein the one or more further therapeutic agents comprises a nucleoside analog, an intercalating agent, or a combination thereof.
18 . (canceled)
19 . The method of claim 17 , wherein the nucleoside analog comprises cytarabine.
20 . The method of claim 17 , wherein the intercalating agent comprises daunorubicin.
21 . The method of claim 16 , wherein the one or more further therapeutic agents comprises a hypomethylating agent.
22 . The method of claim 21 , wherein the hypomethylating agent comprises decitabine or azacytidine.
23 . The method of claim 1 , wherein the hematologic cancer is acute myeloid leukemia.
24 . The method of claim 23 , wherein the acute myeloid leukemia is relapsed or refractory acute myeloid leukemia.
25 - 80 . (canceled)