Combination of T-cell checkpoint inhibitors with inhibitors of e-selectin or CXCR4, or with heterobifunctional inhibitors of both E-selectin and CXCR4

A method for treating a cancer chosen from multiple myeloma, acute lymphocytic leukemia, acute myeloid leukemia, colorectal cancer, and prostate cancer comprising administering to a subject in need thereof:

• (1) an effective amount of pembrolizumab;
• and
• (2) an effective amount of at least one heterobifunctional inhibitor chosen from compounds of Formula (II):
• isomers of compounds of Formula (II), tautomers of compounds of Formula (II), and pharmaceutically acceptable salts of any of the foregoing, wherein:
• R1 is chosen from H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C2-8 haloalkenyl, and C2-8 haloalkynyl groups;
• R2 is chosen from —OH, —NH2, —OC(═O)Y1, —NHC(═O)Y1, and —NHC(═O)NHY1 groups, wherein Y1 is chosen from C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C2-8 haloalkenyl, C2-8 haloalkynyl, C6-18 aryl, and C1-13 heteroaryl groups;
• R3 is chosen from —CN, —CH2CN, and —C(═O)Y2 groups, wherein Y2 is chosen from C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, —OZ1, —NHOH, —NHOCH3, —NHCN, and —NZ1Z2 groups, wherein Z1 and Z2, which may be identical or different, are independently chosen from H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C2-8 haloalkenyl, and C2-8 haloalkynyl groups, wherein Z1 and Z2 may together form a ring;
• R4 is chosen from C3-8 cycloalkyl groups;
• R5 is independently chosen from H, halogen, C1-8 alkyl C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C2-8 haloalkenyl, and C2-8 haloalkynyl groups;
• n is chosen from integers ranging from 1 to 4;
• and
• Linker is chosen from linker groups.