METHODS OF TREATING DLBCL USING BTK INHIBITORS AND COMBINATIONS THEREOF
It provides methods of treating no-GCB DLBCL with (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4, 5, 6, 7-tetrahydropyrazolo-[1, 5-a] pyrimidine-3-carboxamide or a pharmaceutically acceptable salt thereof. It provides methods of treating non-GCB DLBCL in a subject, comprising administering to the subject in need thereof (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4, 5, 6, 7-tetrahydropyrazolo-[1, 5-a] pyrimidine-3-carboxamide or a pharmaceutically acceptable salt thereof, in combination with an anti-CD20 antibody.
1 . A method of increasing the response of a cancer patient for treatment with a BTK inhibitor, the method comprising:
a) administration of a BTK inhibitor to the patient;
b) assaying for gene expression of PAX5, CD79B mutation or NOTH1 mutation in a cancer sample obtained from the patient;
c) comparing the gene expression of PAX5, CD79B mutation or NOTH1 mutation in the cancer sample obtained from a patient treated with a BTK inhibitor with that of a cancer sample prior to BTK inhibitor administration;
d) wherein increased expression of PAX5, CD79B mutation or NOTH1 mutation indicates that the patient will be sensitive to BTK inhibitor treatment.
2 . The method of claim 1 , wherein the BTK inhibitor is Compound 1.
3 . The method of claim 2 , wherein Compound 1 is administered at 320 mg once daily.
4 . The method of claim 2 , wherein Compound 1 is administered at 160 mg twice daily.
5 . The method of claim 3 or 4 wherein Compound 1 is administered in 28 day cycles.
6 . The method of claim 1 , wherein the cancer sample is taken from a patient with non-GCB-DLBCL.
7 . The method of claim 1 , wherein the cancer sample is taken from a patient with ABC-DLBCL.
8 . A method of increasing the response of a cancer patient for treatment with a BTK inhibitor in combination with an anti-CD20 antibody, the method comprising:
a) administration of a BTK inhibitor in combination with an anti-CD20 antibody to the patient;
b) assaying for gene expression of any one of PIM1, BCL2, FOXP1, MYC or CD79B mutation in a cancer sample obtained from the patient;
c) comparing the gene expression of any one of PIM1, BCL2, FOXP1, MYC or CD79B mutatiin the cancer sample obtained from a patient treated with a BTK inhibitor in combination with an anti-CD20 antibody with that of a cancer sample prior to BTK inhibitor in combination with an anti-CD20 antibody administration;
d) wherein increased expression of PIM1, BCL2, FOXP1, MYC or CD79B mutation indicates that the patient will be sensitive to BTK inhibitor treatment.
9 . The method of claim 8 , wherein the BTK inhibitor is Compound 1.
10 . The method of claim 9 , wherein Compound 1 is administered at 320 mg once daily.
11 . The method of claim 9 , wherein Compound 1 is administered at 160 mg twice daily.
12 . The method of claim 10 or 11 wherein Compound 1 is administered in 28 day cycles.
13 . The method of claim 8 , wherein the anti-CD20 antibody is rituximab, ibritumomab tiuxetan, tositumomab, ofatumumab or obinutuzumab.
14 . The method of claim 13 , wherein the anti-CD20 antibody is rituximab.
15 . The method of claim 13 , wherein the anti-CD20 antibody is obinutuzumab.
16 . The method of claim 8 , wherein expression of PIM1 and BCL2 is increased.
17 . The method of claim 8 , wherein expression of PIM1, BCL2 and FOXP1 is increased.
18 . The method of claim 8 , wherein expression of PIM1, BCL2, FOXP1 and MYC is increased.
19 . The method of claim 8 , wherein the cancer sample is taken from a patient with non-GCB-DLBCL.
20 . The method of claim 8 , wherein the cancer sample is taken from a patient with ABC-DLBCL.