Anti-neoplastic combinations and dosing regimens using CDK4/6 inhibitor compounds to treat RB-positive tumors
View Patent ↗This invention directed to methods for treating select RB-positive cancers and other Rb-positive abnormal cellular proliferative disorders using CDK4/6 inhibitors in specific dosing and combination or alternation regimes. In one aspect, treatments of select RB-positive cancers are disclosed using specific CDK4/6 inhibitors in combination or alternation with another chemotherapeutic, for example, an additional kinase inhibitor, PD-1 inhibitor, or BCL-2 inhibitor, or combination thereof.
1. A method for the treatment of a hematological malignancy in a host in need thereof comprising administering an effective amount of Bruton's tyrosine kinase (BTK) inhibitor selected from ibrutinib and acalabrutinib in combination with a CDK 4/6 inhibitor compound of the formula
or a pharmaceutically acceptable salt thereof; and wherein the hematological malignancy is mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), or Waldenstrom's macroglobulinemia.
2. The method of claim 1 , wherein the host is a human.
3. The method of claim 2 , wherein the hematological malignancy is mantle cell lymphoma (MCL).
4. The method of claim 2 , wherein the hematological malignancy is chronic lymphocytic leukemia (CLL).
5. The method of claim 2 , wherein the hematological malignancy is Waldenstrom's macroglobulinemia.
6. The method of claim 2 , wherein the Bruton's tyrosine kinase (BTK) inhibitor is ibrutinib.
7. The method of claim 6 , wherein the hematological malignancy is mantle cell lymphoma (MCL).
8. The method of claim 6 , wherein the hematological malignancy is chronic lymphocytic leukemia (CLL).
9. The method of claim 6 , wherein the hematological malignancy is Waldenstrom's macroglobulinema.
10. The method of claim 2 , wherein the Bruton's tyrosine kinase (BTK) inhibitor is acalabrutinib.
11. The method of claim 10 , wherein the hematological malignancy is mantle cell lymphoma (MCL).
12. The method of claim 10 , wherein the hematological malignancy is chronic lymphocytic leukemia (CLL).
13. The method of claim 10 , wherein the hematological malignancy is Waldenstrom's macroglobulinema.