Methods of treating myelodysplastic syndrome
This disclosure provides methods of treating a myelodysplastic syndrome (MDS) in a subject that is naive to treatment with an agent selected from a hypomethylating agent (HMA) and lenalidomide, or both. The method includes administering to the subject an effective amount of a telomerase inhibitor, such as e.g. imetelstat or imetelstat sodium. In some cases, the subject treated is classified as low or intermediate-1 IPSS risk MDS and/or have MDS relapsed/refractory to Erythropoiesis-Stimulating Agent (ESA).
1. A method of treating a myelodysplastic syndrome (MDS) in a subject, the method comprising:
classifying the subject as being naïve to treatment with an agent selected from a hypomethylating agent (HMA), lenalidomide, and combination thereof;
selecting the subject for treatment with a telomerase inhibitor because the subject has been classified as being naive to treatment with the agent; and
administering an effective amount of the telomerase inhibitor to the subject to treat the myelodysplastic syndrome.
2. The method of claim 1 , wherein the MDS is relapsed or refractory MDS.
3. The method of claim 2 , wherein the MDS is MDS relapsed or refractory to an erythropoiesis-stimulating agent (ESA).
4. The method of claim 1 , wherein the subject is classified as a low or intermediate-1 IPSS risk MDS subject.
5. The method of claim 1 , wherein the subject is transfusion dependent.
6. The method of claim 5 , wherein the transfusion dependent subject has a transfusion requirement of about 4 units or more during the 8 weeks prior to the administration of the telomerase inhibitor.
7. The method of claim 1 , wherein the subject is a non-del5q human patient.
8. The method of claim 1 , wherein the subject is classified as a low or intermediate-1 IPSS risk MDS subject and is non-del5q.
9. The method of claim 1 , wherein the subject is naive to treatment with lenalidomide.
10. The method of claim 1 , wherein the subject is naive to treatment with a hypomethylating agent (HMA).
11. The method of claim 1 , wherein the subject is naive to treatment with lenalidomide and to a hypomethylating agent (HMA).
12. The method of claim 10 , wherein the HMA is decitabine.
13. The method of claim 10 , wherein the HMA is azacitidine.
14. The method of claim 1 , wherein the telomerase inhibitor is imetelstat.
15. The method of claim 14 , wherein the imetelstat is imetelstat sodium.
16. The method of claim 14 , wherein the telomerase inhibitor is imetelstat and is administered for 1, 2, 3, 4, 5, 6, 7, 8 or more than 8 dosage cycles, each cycle comprising:
(a) intravenous administration of about 7-10 mg/kg imetelstat once every four weeks;
(b) intravenous administration of about 7-10 mg/kg imetelstat once weekly for four weeks;
(c) intravenous administration of about 2.5-10 mg/kg imetelstat once every three weeks; or
(d) intravenous administration of about 0.5-9.4 mg/kg imetelstat once every four weeks.
17. The method of claim 16 , wherein each dosage cycle comprises intravenous administration of about 7-10 mg/kg imetelstat once every four weeks.
18. The method of claim 17 , wherein each dosage cycle comprises intravenous administration of about 7.5 mg/kg imetelstat once every four weeks.
19. The method of claim 1 , wherein the MDS is relapsed or refractory MDS and wherein the subject is classified as a low or intermediate-1 IPSS risk MDS subject.
20. The method of claim 14 , wherein the subject is transfusion dependent.
21. The method of claim 14 , wherein the subject is a non-del5q human patient.
22. A method of treating a myelodysplastic syndrome (MDS) in a subject, the method comprising:
classifying the subject as being a non-del5q human subject;
selecting the subject for treatment with a telomerase inhibitor because the subject has been classified as being a non-del5q human subject; and
administering an effective amount of the telomerase inhibitor to the subject to treat the myelodysplastic syndrome.
23. The method according to claim 22 , wherein the MDS is relapsed or refractory MDS.
24. The method according to claim 23 , wherein the MDS is MDS relapsed or refractory to an erythropoiesis-stimulating agent (ESA).
25. The method according to claim 22 , wherein the subject is classified as a low or intermediate-1 IPSS risk MDS subject.
26. The method according to claim 22 , wherein the subject is transfusion dependent.
27. The method according claim 26 , wherein the transfusion dependent subject has a transfusion requirement of about 4 units or more during the 8 weeks prior to the administration of the telomerase inhibitor.
28. The method of claim 23 , wherein the subject is naive to treatment with lenalidomide.
29. The method of claim 23 , wherein the subject is naive to treatment with a hypomethylating agent (HMA).
30. The method of claim 23 , wherein the subject is naive to treatment with lenalidomide and to a hypomethylating agent (HMA).
31. The method of claim 29 , wherein the HMA is decitabine.
32. The method of claim 29 , wherein the HMA is azacitidine.
33. The method according to claim 23 , wherein the telomerase inhibitor is imetelstat.
34. The method according to claim 33 , wherein the imetelstat is imetelstat sodium.
35. The method according to claim 33 , wherein the MDS is relapsed or refractory MDS and wherein the subject is classified as a low or intermediate-1 IPSS risk MDS subject.
36. The method according to claim 33 , wherein the subject is transfusion dependent.
37. The method according to claim 33 , wherein the telomerase inhibitor is imetelstat wherein the use comprises administration for 1, 2, 3, 4, 5, 6, 7, 8 or more than 8 dosage cycles, each cycle comprising:
(a) intravenous administration of about 7-10 mg/kg imetelstat once every four weeks;
(b) intravenous administration of about 7-10 mg/kg imetelstat once weekly for four weeks;
(c) intravenous administration of about 2.5-10 mg/kg imetelstat once every three weeks; or
(d) intravenous administration of about 0.5-9.4 mg/kg imetelstat once every four weeks.
38. The method according to claim 37 , wherein each dosage cycle comprises intravenous administration of about 7-10 mg/kg imetelstat once every four weeks.
39. The method according to claim 38 , wherein each dosage cycle comprises intravenous administration of about 7.5 mg/kg imetelstat once every four weeks.