What do we know about Treanda’s activity in myeloma?
Treanda’s activity in myeloma is being observed from research and studies conducted in Europe. In the laboratory, Treanda appears to be active against myeloma cells that are resistant to other agents. Benadmustine has been evaluated and used alone and in combination with other myeloma agents.
Newly Diagnosed Disease
The combination of bendamustine and prednisone was found to be more effective than the standard combination melphalan and prednisone (MP) in patients with newly diagnosed myeloma in a phase III study. Bendamustine-prednisone therapy resulted in a higher overall response rate, a significantly higher complete response rate (32% vs. 13% with MP), and a longer time to disease progression.
Treanda is being evaluated in combination with Velcade and dexamethasone (BBD) in patients who are not candidates for high-dose chemotherapy and autologous stem cell transplant. Preliminary results from this phase II trial show a high overall response rate with the three-drug combination.
Bendamustine was also added to high-dose melphalan to see if its effect on blood counts would enhance response following stem cell transplantation. Promising results without unexpected side effects were seen in a Phase I study.
Bendamustine has been used in Europe in relapsed/refractory disease in a number of ways, including:
- As a single agent
- In combination with a corticosteroid (prednisolone) and
- In combination with Velcade or Thalomid and dexamethasone
Recent trials have demonstrated the safety and efficacy of various bendamustine combinations in relapsed and/or refractory disease. For example:
An analysis of French data showed that the combination of bendamustine and prednisone or dexamethasone was effective in patients with disease that was refractory to all approved myeloma drugs. Thirty percent of patients responded to therapy.
Treanda, Revlimid, and dexamethasone was shown to be safe and highly effective two Phase I/II trials, with overall response rates of over 50% seen.
In one trial, the combination was effective even in older patients up to 80 years of age, in patients who were heavily pretreated, and in patients who had previously received Revlimid. Because the regimen resulted in very low white blood cell counts, it was suggested that patients also receive a colony stimulating factor to help prevent this side effect. Researchers noted that the side effect profile of this combination makes it an attractive option for patients with pre-existing therapy-related peripheral neuropathy.
In a Phase II study, Treanda plus Velcade and dexamethasone was shown to be effective in patients who had received one or more prior therapies. A response rate of 68% was seen, including 21% complete responses. Low blood counts were the primary severe side effects seen.
In addition, the combination of bendamustine, Thalomid, and dexamethasone has been shown to be a useful regimen for extensively pre-treated patients with prior exposure to Velcade and Revlimid, as well as an effective and well-tolerated therapy for myeloma patients with reduced kidney function.
Treanda, alone or in combination with Revlimid-dexamethasone, is listed as a treatment option for relapsed/refractory myeloma in myeloma treatment guidelines.