Thalidomide Derivative CC-5013 Produces Responses in Refractory Multiple Myeloma

Thalidomide Derivative CC-5013 Produces Responses in Refractory Multiple Myeloma.

According to a recent article published in the journal Blood, the thalidomide derivative CC-5013 appears to produce anti-cancer responses in a significant number of patients with multiple myeloma who have stopped responding to standard therapies.

Multiple myeloma is a cancer involving important immune (infection-fighting) cells called plasma cells. Plasma cells aid the body in fighting infection by producing specialized proteins called antibodies that have the ability to target and/or kill foreign cells. In multiple myeloma, cancerous plasma cells produce abnormal and excessive antibodies that do not have the ability to properly fight infection. In addition, the cancerous plasma cells accumulate in the bone marrow suppressing the normal formation and function of other cells that are necessary for normal production of blood cells and immune functions. The excessive accumulation of cancer cells in the bone marrow ultimately leads to the formation of tumors in the bone and to the breakdown of bone. Standard treatment for multiple myeloma is chemotherapy and may include an autologous or allogeneic stem cell transplant.

Patients with multiple myeloma who stop responding to standard therapies are considered to have resistant or refractory disease and effective treatment options are limited. Thalidomide has recently been evaluated for the treatment of multiple myeloma, renal cell carcinoma and various types of cancers. Researchers speculate that thalidomide produces anti-cancer responses through several biological mechanisms. However, thalidomide is associated with side effects such as neuropathy (loss of sensation, particularly in extremeties), severe fatigue and constipation. Researchers have been evaluating different forms of thalidomide, called immunomodulatory derivatives of thalidomide (IMiDs) in the treatment of cancer, which have demonstrated promise in delivering cancer therapy as well as reducing some of the side effects caused by thalidomide.

An early-phase clinical trial recently conducted by researchers from the Dana-Farber Cancer Institute evaluated an IMiD called CC-5013 in the treatment of patients with resistant multiple myeloma. This trial included 24 patients with refractory multiple myeloma at an average age of 57 years, with each patient previously treated with an average number of three therapies. Following therapy with CC-5013, 71% of patients achieved an anti-cancer response and 8% of patients achieved disease stabilization. The average duration of response was 6 months. The optimal dose of CC-5013 was established in this clinical trial, which proved to be well tolerated, with no significant somnolence, constipation or neuropathy.

These researchers concluded that CC-5013 appears to be an effective and well tolerated treatment strategy for patients with refractory multiple myeloma. The researchers also state that future clinical trials evaluating CC-5013 earlier in the course of disease either alone or in combination with other therapies are warranted. Patients with refractory multiple myeloma may wish to speak with their physician about the risks and benefits of participating in a clinical trial further evaluating CC-5013 or other promising therapies.

Reference: Richardson P, SchlossmanR, Weller E, et al. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma.

Blood. 2002;100: 3063-3067.

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