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 for treating a hematologic cancer in a patient in need thereof, the method comprising
administering a treatment regimen comprising alvocidib to a patient having a bone marrow NOXA priming value of at least 15%, the bone marrow NOXA priming value having been obtained by an in vitro method comprising:
i) permeabilizing a hematologic cancer cell obtained from bone marrow of the patient, thereby producing a permeabilized hematologic cancer cell; and
ii) contacting the permeabilized hematologic cancer cell with a NOXA BH3 domain peptide.
2. The method of claim 1 , wherein the patient has a bone marrow NOXA priming value of least 20%.
3. The method of claim 1 , wherein the patient has a bone marrow NOXA priming value of at least 30%.
4. The method of claim 1 , wherein the patient has a bone marrow NOXA priming value of at least 40%.
5. The method of claim 1 , wherein the patient's cytogenetics are high risk.
6. The method of claim 1 , wherein the treatment regimen is administered to the patient only if the patient has a prior history of myelodysplasic syndrome (MDS).
7. The method of claim 1 , wherein the NOXA BH3 domain peptide is used at a concentration ranging from 0.1 μM to 200 μM.
8. The method of claim 1 , wherein the hematologic cancer is selected from the group consisting of acute myelogenous leukemia (AML), multiple myeloma, follicular lymphoma, acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia, and non-Hodgkin's lymphoma.
9. The method of claim 8 , wherein the hematological cancer is acute myelogenous leukemia (AML).
10. The method of claim 1 , wherein the hematologic cancer is myelodysplasic syndrome (MDS) or chronic lymphocytic leukemia (CLL).
11. The method of claim 1 , wherein the treatment regimen comprises alvocidib, cytarabine, and mitoxantrone (FLAM).
12. The method of claim 1 , wherein the bone marrow sample is derived from the biopsy of a patient with multiple myeloma, acute myelogenous leukemia, acute lymphocytic leukemia, chronic lymphogenous leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma or non-Hodgkin's lymphoma.