Thalidomide Not Associated with Survival Improvement in Multiple Myeloma

Thalidomide Not Associated with Survival Improvement in Multiple Myeloma

According to an article recently published in the New England Journal of Medicine, the addition of thalidomide to autologous stem cell transplantation does not improve survival for patients with newly diagnosed multiple myeloma.

Multiple myeloma is a cancer of the blood that affects the plasma cells. Plasma cells are an important part of the immune system; they produce antibodies to help fight infection and disease. Multiple Myeloma is characterized by an excess production of abnormal plasma cells. Symptoms include increased risk of bacterial infections and impaired immune responses.

Myeloma may also damage the kidneys and cause osteoporosis, anemia, and an elevated blood calcium level.

In a stem cell transplant (an important part of myeloma treatment), high doses of therapy are used to kill more cancer cells than conventional doses. Unfortunately, the higher doses tend to destroy important hematopoietic stem cells (immature blood cells). These stem cells mature into the following: red blood cells, which transport oxygen and nutrients to tissues in the body; white blood cells, which help the body fight infection; and platelets, which aid the blood in clotting. Low levels of hematopoietic stem cells caused by high-dose treatment can result in life-threatening conditions.

There are two general types of stem cell transplants: an autologous transplant and an allogeneic transplant. During an autologous transplant, the patients own hematopoietic stem cells are collected prior to therapy, frozen, and then re-infused following high-dose treatment.

Unfortunately, a significant portion of patients still experience a cancer recurrence following treatment with high-dose therapy and stem cell transplantation. Researchers continue to evaluate ways to reduce these recurrences with the goal of improving overall survival for patients with multiple myeloma.

Thalidomide is an agent that has demonstrated anticancer activity in patients with multiple myeloma that has stopped responding to standard therapies. Thalidomide is an immunomodulatory agent that helps the immune system fight cancer. In addition, thalidomide stops or prevents blood vessels from growing and providing cancer cells with nutrients and oxygen for their spread and growth.

Researchers from the University of Arkansas conducted a trial to evaluate the potential benefits of thalidomide when used in addition to autolgous stem cell transplantation in patients with newly diagnosed multiple myeloma. This trial included 668 patients who were treated between 1998 and 2004. All patients were treated with melphalan-based intensive chemotherapy followed by autologous stem cell transplantation; approximately half of the patients also received thalidomide during treatment (thalidomide was continued until cancer progression or intolerable side effects).

Thalidomide did not improve overall survival at 5 years:

  • Complete disappearances of cancer occurred in 62% of patients who received thalidomide, compared with 43% of patients who did not receive thalidomide.
  • At 5 years, 56% of patients who received thalidomide survived without recurrence (event-free survival), compared to 44% for patients who did not receive thalidomide.
  • At 5 years, overall survival was approximately 65% for both groups of patients.
  • If a patient experienced a cancer recurrence following therapy, the median survival time following the recurrence was 1.1 years for those treated with thalidomide, and 2.7 years for those not treated with thalidomide.
  • Side effects including blood clots (34% for those treated with thalidomide vs. 18% for those not treated with thalidomide), severe peripheral neuropathy (burning, tingling, loss of sensation in extremities), obstruction of the bowel, fainting, and low levels of immune cells were significantly more common among patients treated with thalidomide compared to those who did not receive thalidomide.

The researchers concluded that, although the addition of thalidomide improved anticancer responses and reduced recurrences at 5 years after treatment, overall survival was not improved with thalidomide in patients with newly diagnosed multiple myeloma undergoing treatment with autologous stem cell transplantation.

The authors state that overall survival differences were owing in part to significantly shorter survival after relapse in the thalidomide group than in the group not treated with thalidomide. Therefore, further study is warranted to evaluate new agents for recurrent multiple myeloma following treatment including thalidomide.

Reference: Barlogie B, Tricot G, Anaissie E, et al. Thalidomide and Hematopoietic-Cell Transplantation for Multiple Myeloma. New England Journal of Medicine. 2006; 354:1021-1030.

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