CPC A61K 31/505 (2013.01) [A61K 31/519 (2013.01); A61K 45/06 (2013.01); A61P 35/00 (2018.01); C07D 239/42 (2013.01); A61K 2300/00 (2013.01)] | 8 Claims |
1. A method for treating chronic lymphocytic leukemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of
(a) a histone deacetylase 6 (HDAC6) selective inhibitor, wherein the HDAC6 inhibitor is Compound B:
or a pharmaceutically acceptable salt thereof; and
(b) a Bruton's tyrosine kinase (BTK) inhibitor or a pharmaceutically acceptable salt thereof;
wherein the BTK inhibitor is ibrutinib or a pharmaceutically acceptable salt thereof;
the HDAC6 selective inhibitor and the BTK inhibitor are each administered in a sub-therapeutically effective amount;
the HDAC6 selective inhibitor and the BTK inhibitor reduce the expression of an inhibitory checkpoint molecule in a T- and/or B-cell compartment in the subject;
wherein the checkpoint molecule is selected from the group consisting of CD274 (PDL-1), CD273 (PDL-2), CD80 (87-1), CD86 (B7-2), CD 152 (CTLA4), CD275 (B7RP1), CD276 (B7-H3), B7-H4 (VTCN1), CD270 (HVEM), BLTA, GAL9, CD366 (TIMS), A2aR, CD279 (PD-1), KIR, and CD223 (LAGS); and
the ratio of Compound B to the BTK inhibitor is 3:1.
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