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1. WO2020223583 - METHODS OF TREATING ACUTE MYELOID LEUKEMIA WITH FARNESYLTRANSFERASE INHIBITORS

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[ EN ]

CLAIMS

We claim:

1. A method of treating an FLT3LG-expressing acute myeloid leukemia (AML) in a

subject, comprising administering a therapeutically effective amount of a

farnesyltransf erase inhibitor (FTI) to the subject.

2. The method of claim 1, wherein the subject further has a CXCR4 expression higher than a reference level.

3. The method of claim 1, wherein the subject further has an activating mutation in the

CXCR4 gene.

4. The method of claim 1, wherein the subject further has a higher ratio of CXCR4 to

CXCR2 expression than a reference ratio.

5. The method of claim 4, wherein the reference ratio is 1/10, 1/9, 1/8, 1/7, 1/6, 1/5, 1/4, 1/3, 1/2, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

6. The method of any one of claims 1 to 5, comprising analyzing the FLT3LG expression in a sample from the subject prior to administration of the FTI to the subject.

7. The method of claim 6, further comprising analyzing the CXCR4 expression and

optionally the CXCR2 expression in the sample.

8. The method of claim 6, further comprising determining the DNA sequence of CXCR4 in the sample.

9. The method of any one of claims 6 to 8, wherein the sample is a bone marrow biopsy, a spinal fluid sample, a liver sample, a testicle sample, a lymph node sample, or a spleen sample.

10. The method of any one of claims 6 to 8, wherein the sample is isolated cells.

11. The method of any one of claims 1 to 10, wherein the subject is transfusion dependent prior to administration of the FTI.

12. The method of claim 11, wherein the method is effective to convert the transfusion dependent subject into a transfusion independent subject.

13. The method of any one of claims 1 to 10, wherein the AML is newly diagnosed AML.

14. The method of any one of claims 1 to 10, wherein the subject having AML is either an elderly patient, unfit for chemotherapy, or with poor-risk AML.

15. The method of any one of claims 1 to 10, wherein the AML is relapsed or refractory AML.

16. The method of any one of claims 1 to 15, wherein the FTI is selected from the group consisting of tipifarnib, arglabin, perrilyl alcohol, SCH-66336, L778123, L739749, FTI- 277, L744832, CP-609,754, R208176, AZD3409, and BMS-214662.

17. The method of claim 16, wherein the FTI is tipifarnib.

18. The method of claim 17, wherein tipifarnib is administered at a dose of 0.05-500 mg/kg body weight.

19. The method of claim 17, wherein tipifarnib is administered twice a day.

20. The method of claim 17, wherein tipifarnib is administered at a dose of 100-1200 mg twice a day.

21. The method of claim 17, wherein the tipifarnib is administered at a dose of 100 mg, 200 mg, 300 mg, 400 mg, 600 mg, 900 mg or 1200 mg twice a day.

22. The method of claim 17, wherein the tipifarnib is administered on days 1-7 and 15-21 of a 28-day treatment cycle.

23. The method of claim 17, wherein the tipifarnib is administered on days 1-21 of a 28-day treatment cycle.

24. The method of claim 17, wherein the tipifarnib is administered on days 1-7 of a 28-day treatment cycle .

25. The method of any one of claims 22 to 24, wherein tipifarnib is administered for at least 1 cycle.

26. The method of claim 25, wherein tipifarnib is administered for at least 3 cycles, 6 cycles, 9 cycles, or 12 cycles.

27. The method of any one of claims 17 to 26, wherein tipifarnib is administered before, during, or after radiation.

28. The method of any one of claims 17 to 26, further comprising administering a

therapeutically effective amount of a second active agent or a support care therapy.