NEWLY DIAGNOSED PATIENTS:

WHAT IS MULTIPLE MYELOMA


Carfilzomib (PR-171)

What is Carfilzomib?

Carfilzomib is an oral proteasome inhibitor being developed by Onyx, with several trials being facilitated by the Multiple Myeloma Research Consortium (MMRC). Carfilzomib is in the same class of agents as Velcade® (bortezomib). Proteasomes are enzymes found in cells and play an important role in regulating cell function and growth by controlling the breakdown of important proteins. Carfilzomib blocks the activity of proteasomes and by blocking the proteasome, it disrupts processes related to the growth and survival of cancer cells. Carfilzomib is also known as PR-171.

What do we know about Carfilzomib activity in myeloma?

Carfilzomib has been shown to have potent anti-myeloma activity in the laboratory and acts synergistically with dexamethasone. It can also overcome the resistance of myeloma cells to other drugs, including Velcade. Carfilzomib displayed anti-tumor effects against various hematologic malignancies, including myeloma, in two Phase I studies.

Results of two Phase II trials that were conducted by members of the MMRC were reported at the American Society of Hematology (ASH) meeting in 2008.

  • In the first trial (PX-171-003), carfilzomib alone led to partial responses in 13% patients with relapsed and refractory myeloma (n=39). Nineteen percent of patients who were refractory to Velcade responded to carfilzomib. The agent was well tolerated for up to a year, with fatigue, anemia, and low platelet counts the most common side effects reported. Click here to view the abstract.
  • In the second trial (PX-171-004), single-agent carfilzomib resulted in an overall response rate of 36% in patients with relapsed myeloma (n=31); 3% of patients achieved a complete response (CR), 7% achieved a very good partial response (VGPR), and 26% achieved a partial response (PR). The overall response rate in patients who had not received prior Velcade therapy was 57%. The agent was well tolerated for up to a year, with fatigue, anemia, and neutropenia being the most commonly reported side effects. Click here to view the abstract.

How is Carfilzomib currently being studied in myeloma?

Carfilzomib is being evaluated in Phase II clinical trials as single-agent therapy in relapsed or relapsed and refractory myeloma (an expansion of the single-agent study described earlier), and in combination with Revlimid and dexamethasone in relapsed myeloma. A Phase I trial is evaluating carfilzomib in patients with relapsed and refractory myeloma who also have impaired kidney function.

Carfilzomib is also being evaluated as maintenance therapy in a Phase II trial in patients who achieved stable disease or better in a prior carfilzomib study.

Click here to go to the MMRF Clinical Trial Matching Service.