Velcade® plus Perifosine Shows Promise in Relapsed or Refractory Multiple Myeloma

Among patients with relapsed or refractory multiple myeloma previously treated with Velcade® (bortezomib), 40% responded to treatment with a combination of Velcade and perifosine. The details of this study were presented at the 2008 meeting of the American Society of Hematology on December 9, 2008 in San Francisco.

Multiple myeloma is a cancer of plasma cells. Plasma cells are a special type of white blood cell that are part of the body’s immune system. Plasma cells normally live in the bone marrow and make proteins called antibodies that circulate in the blood and help fight certain types of infections. Plasma cells also play a role in the maintenance of bone by secretion of a hormone, called osteoclast activating factor, which causes the breakdown of bone. Patients with multiple myeloma have increased numbers of abnormal plasma cells that may produce increased quantities of dysfunctional antibodies detectable in the blood and/or urine. These abnormal antibodies are referred to as paraproteins or monoclonal proteins in the blood (M proteins) or urine (Bence Jones protein).

Velcade-a drug used in the treatment of multiple myeloma-is a proteosome inhibitor. Proteosomes are proteins found in virtually all cells. They are responsible for the breakdown and reuse of a cell’s other proteins. Proteosomes regulate several aspects of cellular activity, including survival. By inhibiting proteosomes, Velcade has demonstrated an ability to reduce cellular survival.

Perifosine is an investigational drug that inhibits cell growth by targeting cell membranes. It has previously shown promise in the treatment of relapsed or refractory multiple myeloma,[1] and laboratory studies suggest that it may work well in combination with Velcade.[2]

The current study involved 76 patients with relapsed or refractory multiple myeloma.[3] All of the patients had received prior therapy with Velcade, and 35 patients were considered refractory to Velcade. Patients were treated with perifosine and Velcade with or without dexamethasone.

Information about response rate (the percent of patients experiencing a reduction in the extent of myeloma) was available for 57 patients. Overall response rate included complete, partial, and minor responses.

  • The overall response rate was 40%.
  • In the subset of patients refractory to Velcade, the overall response rate was 37%.
  • The combination of Velcade and perifosine was described as well tolerated.

These data suggest that perifosine may be a useful new agent for the treatment of patients with multiple myeloma.


[1] Richardson P, Lonial S, Jakubowiak A, et al. Multi-center phase II study of perifosine (KRX-0401) alone and in combination with dexamethasone (dex) for patients with relapsed/refractory multiple myeloma (MM): Promising activity as combination therapy with manageable toxicity. Blood. 2007;110, abstract number 1164.

[2] Hideshima T, Catley L, Yasui H, et al. Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells. Blood. 2006;107:4053-4062.

[3] Richardson P, Wolf J, Jakubowiak et al. Phase I/II results of a multicenter trial of perifosine (KRX-0401) + bortezomib in patients with relapsed or relapsed/refractory multiple myeloma who were previously relapsed from or refractory to bortezomib. Blood. 2008;112:321, abstract number 870.

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