METHODS OF TREATING ABC-DLBCL USING INHIBITORS OF BRUTON'S TYROSINE KINASE

• US 20120071497A1
• Filed: 06/03/2011
• Published: 03/22/2012
• Est. Priority Date: 06/03/2010
• Status: Abandoned Application

• Current Assignee: Pharmacyclics LLC (Abbvie Incorporated)
• Original Assignee: Pharmacyclics Incorporated (Abbvie Incorporated)
• Inventors: Buggy, Joseph J., Staudt, Louis Michael, Wilson, Wyndham Hopkins
• Application Number:
  US13/153,291
• Publication Number:
  US 20120071497A1
• Time in Patent Office: Days
• US Class Current: 514/262.1
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574

Abstract

Disclosed herein are methods for treating an individual diagnosed with ABC-DLBCL. The methods include administering to the individual an inhibitor of Bruton'"'"'s tyrosine kinase (Btk).

Claims

1. A method for treating diffuse large B-cell lymphoma, activated B cell-like subtype (ABC-DLBCL), in an individual in need thereof, comprising:

administering to the individual a therapeutically effective amount of an inhibitor of Bruton'"'"'s tyrosine kinase.

2. The method of claim 1, further comprising diagnosing the individual with diffuse large B-cell lymphoma, activated B cell-like subtype (ABC-DLBCL), by determining the gene sequence of one or more biomarkers in a plurality of lymphoid cells isolated from the diffuse large B-cell lymphoma.

3. The method of claim 1, wherein the Activated B cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) is characterized by a CD79B mutation.

4. The method of claim 3, wherein the CD79B mutation is a mutation of the immunoreceptor tyrosine-based activation motif (ITAM) signaling module.

5. The method of claim 3, wherein the CD79B mutation is a missense mutation of the first immunoreceptor tyrosine-based activation motif (ITAM) tyrosine.

6. The method of claim 3, wherein the CD79B mutation increases surface BCR expression and attenuates Lyn kinase activity.

7. The method of claim 1, wherein the Activated B cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) is characterized by a CD79A mutation.

8. The method of claim 7, wherein the CD79A mutation is in the immunoreceptor tyrosine-based activation motif (ITAM) signaling module.

9. The method of claim 7, wherein the CD79A mutation is a splice-donor-site mutation of the immunoreceptor tyrosine-based activation motif (ITAM) signaling module.

10. The method of claim 7, wherein the CD79A mutation deletes the immunoreceptor tyrosine-based activation motif (ITAM) signaling module.

11. The method of claim 7, wherein the Activated B cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) is characterized by a mutation in MyD88, A20, or a combination thereof.

12. The method of claim 11, wherein the MyD88 mutation is the amino acid substitution L265P in the MYD88 Toll/IL-1 receptor (TIR) domain.

13. The method of claim 1, wherein the inhibitor of Bruton'"'"'s tyrosine kinase is a reversible inhibitor.

14. The method of claim 1, wherein the inhibitor of Bruton'"'"'s tyrosine kinase is an irreversible inhibitor.

15. The method of claim 1, wherein the inhibitor of Bruton'"'"'s tyrosine kinase forms a covalent bond with a cysteine sidechain of a Bruton'"'"'s tyrosine kinase, a Bruton'"'"'s tyrosine kinase homolog, or a Btk tyrosine kinase cysteine homolog.

16. The method of claim 1, wherein the inhibitor of Bruton'"'"'s tyrosine kinase has the structure of Formula (D):

17. The method of claim 1 wherein the Bruton'"'"'s tyrosine kinase inhibitor is (R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one.