TREATMENT OF MULTIPLE MYELOMA
The present disclosure provides methods of treating multiple myeloma in a patient in need thereof comprising administering a gamma secretase and a B-cell maturation antigen (BCMA)-directed therapy to the patient.
1 . A method of treating multiple myeloma comprising administering a gamma secretase inhibitor to a patient in need thereof wherein (a) an amount of B-cell maturation antigen expressed on malignant plasma cell is increased by about 5% to about 70%, (b) an amount of B-cell maturation antigen expressed is about 90% on malignant plasma cells of the patient. (c) an amount of B-cell maturation antigen expressed is more than 50% on malignant plasma cells of the patient, (d) an amount of B-cell maturation antigen receptor density of the patient is increased by more than 5-fold, or (e) an amount of soluble B-cell maturation antigen of the patient is reduced by more than 5%.
2 - 5 . (canceled)
6 . The method of claim 1 , wherein the amount of B-cell maturation antigen expressed by the patient is determined from a blood sample of the patient.
7 . The method of claim 1 , wherein the amount of B-cell maturation antigen expressed by the patient is determined by flow cytometry.
8 . The method of claim 1 , wherein the gamma-secretase inhibitor is selected from the group consisting of nirogacestat, crenigacestat, AL101, AL102, semagacestat, avagacestat, and ianabecestat, or pharmaceutically acceptable salt thereof.
9 . The method of claim 1 , wherein the gamma-secretase inhibitor is nirogacestat or pharmaceutically acceptable salt thereof.
10 - 20 . (canceled)
21 . A method for treating multiple myeloma in a patient in need thereof comprising administering to the patient an oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof wherein the oral dosage provides a mean maximum drug plasma concentration (C max ) of more than 225 ng/ml.
22 - 23 . (canceled)
24 . A method for treating multiple myeloma in a patient in need thereof comprising administering of the patient an oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof in combination with a B-cell maturation antigen (BCMA)-directed therapy to the patient.
25 . The method of claim 24 , wherein the BCMA-directed therapy is one or more of an allogenic chimeric antigen receptor T cell therapy, an autologous chimeric antigen receptor T cell therapy, an immunotherapy, an antibody drug conjugate therapy, or a bispecific antibody therapy9 with dual specificity for BCMA and an immune-related target.
26 . A method for treating multiple myeloma in a patient in need thereof comprising administering to the patient an oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof in combination with belantamab mafodotin.
27 . The method of claim 8 , wherein the nirogacestat, or pharmaceutically acceptable salt thereof, is nirogacestat hydrobromide.
28 . The method of claim 27 , wherein the nirogacestat hydrobromide is nirogacestat dihydrobomide.
29 - 39 . (canceled)
40 . The method of claim 1 , wherein the patient is human.