Predicting response to alvocidib by mitochondrial profiling
The present disclosure provides diagnostic methods useful for predicting a patient's response to alvocidib and guiding a physician decision to administer alvocidib to the patient.
1. A method of treating a mammal with acute myeloid leukemia (AML) whose disease is dependent on MCL-1 comprising administering alvocidib, cytarabine, and mitoxantrone to the mammal with bone marrow cells having MCL-1 priming of at least 15% determined by subjecting cells from the mammal's bone marrow to a BH3 mimetic that is selective for MCL-1 and determining the percentage change in the mitochondrial polarization which corresponds to the MCL-1 priming.
2. The method of claim 1 , wherein the determination of MCL-1 priming includes permeabilizing the bone marrow cells.
3. The method of claim 1 wherein the AML is refractory.
4. The method of claim 1 wherein the AML is relapsed or refractory.
5. The method of claim 1 wherein the MCL-1 priming is at least 20%.
6. The method of claim 1 wherein the MCL-1 priming is at least 25%.
7. The method of claim 1 wherein the MCL-1 priming is at least 30%.
8. The method of claim 1 wherein the MCL-1 priming is at least 35%.
9. A method of treating a mammal with acute myeloid leukemia (AML) whose disease is dependent on MCL-1 comprising:
acquiring a plurality of bone marrow cells from the mammal;
determining an MCL-1 priming of the bone marrow cells determined by subjecting cells from the mammal's bone marrow to a BH3 mimetic that is selective for MCL-1 and determining the percentage change in the mitochondrial depolarization which corresponds to the MCL-1 priming; and
administering alvocidib, cytarabine, and mitoxantrone to the mammal if the bone marrow cells have the MCL-1 priming of at least 15%.
10. The method of claim 9 wherein the determination of MCL-1 priming includes permeabilizing the bone marrow cells.
11. The method of claim 9 wherein the AML is refractory.
12. The method of claim 9 wherein the AML is relapsed or refractory.
13. The method of claim 9 wherein the MCL-1 priming is at least 20%.
14. The method of claim 9 wherein the MCL-1 priming is at least 25%.
15. The method of claim 9 wherein the MCL-1 priming is at least 30%.
16. The method of claim 9 wherein the MCL-1 priming is at least 35%.