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, the method comprising:
administering an effective amount of a therapeutic agent having inhibitory activity against Janus kinase 2 (JAK2) and fms-like tyrosine kinase 3 (FLT3) to a subject having a predetermined genetic profile comprising an FLT3 mutation.
2 . The method of claim 1 , wherein the FLT3 mutation comprises an internal tandem duplication (ITD) mutation.
3 . The method of claim 1 , wherein the FLT3 mutation comprises a tyrosine kinase domain (TKD) mutation.
4 . The method of claim 3 , wherein the TKD mutation is a FLT 835 mutation.
5 - 6 . (canceled)
7 . The method of claim 3 , wherein the TKD mutation comprises an FLT3 691 mutation.
8 - 9 . (canceled)
10 . The method of claim 1 , wherein the FLT3 mutation comprises ITD-835H, ITD-835V, ITD-D835Y, or ITD-F691L.
11 . (canceled)
12 . The method of claim 1 , wherein the therapeutic agent is pacritinib, or a pharmaceutically acceptable salt, prodrug, or N-oxide thereof.
13 - 15 . (canceled)
16 . The method of claim 1 , wherein the method further comprises administering an effective amount of a nucleoside analog, an intercalating agent, a hypomethylating agent, or combinations thereof.
17 - 18 . (canceled)
19 . The method of claim 16 , wherein the nucleoside analog comprises cytarabine.
20 . The method of claim 16 , wherein the intercalating agent comprises daunorubicin.
21 . (canceled)
22 . The method of claim 16 , wherein the hypomethylating agent comprises decitabine or azacytidine.
23 . The method of claim 1 , wherein the hematologic cancer comprises acute myeloid leukemia.
24 . (canceled)
25 . A method for treating acute myeloid leukemia, the method comprising:
administering an effective amount of pacritinib, or a pharmaceutically acceptable salt, prodrug, or N-oxide thereof to a subject having a predetermined mutation in FLT3, the mutation comprising:
i. an internal tandem duplication (ITD) mutation; and/or
ii. a tyrosine kinase domain (TKD) mutation.
26 . The method of claim 25 , wherein the FLT3 mutation comprises an ITD mutation and a TKD mutation.
27 - 36 . (canceled)
37 . The method of claim 25 , wherein the method further comprises administering an effective amount of a nucleoside analog, an intercalating agent, a hypomethylating agent, or combinations thereof.
38 - 43 . (canceled)
44 . The method of claim 25 , wherein the acute myeloid leukemia is relapsed or refractory acute myeloid leukemia.
45 . A method of selecting a treatment regimen for a subject in need of treatment for a hematologic cancer, the method comprising:
receiving a genetic profile for the subject, the genetic profile comprising an FLT3 mutation; and
selecting a treatment regimen based on the genetic profile, the treatment regimen comprising a therapeutic agent having inhibitory activity against Janus kinase 2 (JAK2) and fms-like tyrosine kinase 3 (FLT3).
46 . (canceled)
47 . The method of claim 45 , wherein the FLT3 mutation is a tyrosine kinase domain (TKD) mutation.
48 - 55 . (canceled)
56 . The method of claim 45 , wherein the therapeutic agent is pacritinib, or a pharmaceutically acceptable salt, prodrug, or N-oxide thereof.
57 - 61 . (canceled)
62 . The method of claim 45 , wherein the treatment regimen further comprises administering a nucleoside analog, an intercalating agent, a hypomethylating agent, or combinations thereof.
63 - 68 . (canceled)
69 . The method of claim 45 , wherein the hematologic cancer comprises acute myeloid leukemia.
70 - 80 . (canceled)