Methods for the identification, evaluation and treatment of patients having multiple myeloma

Patent metadata

Field	Value
Publication number	US-11268154-B2
Application number	US-201615772954-A
Country	US
Kind code	B2
Filing date	Nov 4, 2016
Priority date	Nov 4, 2015
Publication date	Mar 8, 2022
Grant date	Mar 8, 2022

Abstract

The present disclosure relates to methods for the treatment of multiple myeloma in patients who have one or more cytogenetic alterations. In particular, the disclosure provides methods for treatment of multiple myeloma in patients who have one or more cytogenetic alternations by administering to a patient a treatment regimen comprising a proteasome inhibitor or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof if said patient is identified as a likely responder to the treatment regimen by assessing the presence of said cytogenetic alterations.

First claim

We claim:

1. A method of treating a patient having multiple myeloma, comprising:
(i) determining that the patient has a cytogenetic alteration at chromosome 17, wherein the cytogenetic alteration at chromosome 17 is del (17), and
(ii) administering to the patient a treatment regimen comprising administering about 5.7 mg, about 4 mg or about 3 mg of a compound of formula (IIIa):

or a pharmaceutically acceptable salt thereof, on days 1, 8 and 15 of a 28-day cycle,
wherein the patient is determined to also have at least one other cytogenetic alteration wherein the at least one other cytogenetic alteration is t(4:14) and/or t(14:16).

2. The method of claim 1 , wherein the deletion at chromosome 17 is del (17p13).

3. The method of claim 1 , wherein the at least one other cytogenetic alteration is t(4:14).

4. The method of claim 1 , wherein the at least one other cytogenetic alteration is t(14:16).

5. The method of claim 1 , wherein the patient is determined to have at least two other cytogenetic alterations wherein the at least two other cytogenetic alterations are t(4:14) and t(14:16).

6. The method of claim 1 , wherein the determining that a patient has a cytogenetic alteration at chromosome 17 comprises the steps of:
(i) providing a bone marrow aspirate sample from the patient;
(ii) isolating CD138 positive plasma cells from the sample; and
(iii) performing FISH analysis on the CD138 enriched positive plasma cells.

7. The method of claim 1 , wherein the compound of formula (IIIa) is in a solid dosage form and the solid dosage form is a capsule.

8. The method of claim 7 , wherein the capsule comprises a mixture of the compound of formula (IIIa) or a pharmaceutically acceptable salt thereof, microcrystalline cellulose, talc, and magnesium stearate.

9. The method of claim 1 , wherein the treatment regimen further comprises lenalidomide and dexamethasone.

10. A method of treating a patient having multiple myeloma, comprising:
i) selecting a patient based upon the patient having a cytogenetic alteration at chromosome 17, wherein the cytogenetic alteration at chromosome 17 is del (17); and
ii) administering to the patient a treatment regimen comprising a compound of formula (IIIa):

or a pharmaceutically acceptable salt thereof,
wherein the patient is determined to also have at least one other cytogenetic alteration wherein the at least one other cytogenetic alteration is t(4:14) and/or t(14:16).

11. The method of claim 10 , wherein the deletion at chromosome 17 is del (17p13).

12. The method of claim 10 , wherein the at least one other cytogenetic alteration is t(4:14).

13. The method of claim 10 , wherein the at least one other cytogenetic alteration is t(14:16).

14. The method of claim 10 , wherein the patient is determined to have at least two other cytogenetic alterations wherein the at least two other cytogenetic alterations are t(4:14) and t(14:16).

15. The method of claim 10 , wherein the selecting a patient based upon the patient having a cytogenetic alteration at chromosome 17 comprises the steps of:
(i) providing a bone marrow aspirate sample from the patient;
(ii) isolating CD138 positive plasma cells from the sample; and
(iii) performing FISH analysis on the CD138 enriched positive plasma cells.

16. The method of claim 10 , wherein the compound of formula (IIIa) is in a solid dosage form and the solid dosage form is a capsule.

17. The method of claim 16 , wherein the capsule comprises a mixture of the compound of formula (IIIa) or a pharmaceutically acceptable salt thereof, microcrystalline cellulose, talc, and magnesium stearate.

18. The method of claim 10 , wherein the compound of formula (IIIa) is administered on each of days 1, 8 and 15 of a 28 day cycle.

19. The method of claim 10 , wherein the treatment regimen further comprises lenalidomide and dexamethasone.

Assignees

• Millennium Pharm Inc
• Celgene Corp
• Takeda Pharmaceuticals Co

Inventors

• Di Bacco Alessandra M
• Mulligan George J

Classifications

• G01N33/57505

  of the blood, e.g. leukaemia · CPC title

• A61K38/05 Primary

  Dipeptides · CPC title

• A61K31/573

  substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone · CPC title

• C12Q1/6886 Primary

  for cancer (immunoassay for cancer G01N33/575) · CPC title

• A61K31/69

  Boron compounds · CPC title