The 10-year follow-up results of a Phase 2 trial suggest that thalidomide increases the median time to disease progression in smoldering multiple myeloma patients who respond to treatment.

However, researchers also observed an increased rate of side effects compared to earlier results. They therefore do not recommend the use of thalidomide in smoldering myeloma patients.

Approximately 10 to 15 percent of all myeloma patients have smoldering myeloma, a slow-growing form of the disease that often appears without symptoms. Approximately 73 percent of patients with smoldering myeloma develop active myeloma within 15 years of diagnosis.

Smoldering myeloma patients may not need treatment immediately. However, the high risk of progression to active myeloma requires them to regularly follow up with a physician to check for changes in their disease status.

Thalidomide ^[1] (Thalomid), which has been used to successfully treat relapsed myeloma patients, functions in part by stopping tumors from forming new blood vessels. Researchers hypothesize that progression to active myeloma from smoldering myeloma may be caused by increased formation of new blood vessels in tumors. Given that possibility, the researchers evaluated thalidomide as a potential therapy for patients with smoldering myeloma.

For their study, the researchers enrolled 29 smoldering and indolent multiple myeloma patients who received 200 mg/day of thalidomide for two weeks. The dose was increased by 200 mg/day for two weeks, as tolerated, to the maximum dose of 800 mg/day.

Study results published in 2003 had shown that at a median follow-up of 2 years, the median time to progression to active myeloma was 22.5 months.

The recent long-term results, at a median follow-up of 10 years, show that 34 percent of patients achieved a partial response to the treatment and 32 percent achieved a minimal response.

The median time to progression to active myeloma was 35 months, but differed significantly based on the patient’s response to treatment. The median time to progression was 61 months in patients who achieved a partial response, 39 months in those who achieved minimal response, and 9 months in patients who did not respond to treatment.

Fifty-five percent of patients experienced severe side effects. The most serious side effects observed included pain and tingling from nerve damage in the limbs (14 percent), infection (13 percent), sedation (7 percent), hypertension (7 percent), and slow heartbeat (7 percent).

The authors noted that “compared with the previous report in 2003, we saw an increase in side effects in many categories with longer duration of therapy.”

The researchers pointed out that the maximum dose of 800 mg/day of thalidomide is now known to cause excessive side effects. They therefore recommended a starting daily dose between 50 mg and 200 mg for future trials evaluating the impact of thalidomide in smoldering myeloma patients to decrease the frequency of side effects.

They added that more clinical trials are needed to investigate the impact of preventive treatment on the progression of smoldering to active myeloma and its impact on overall survival.

For more information about this study, please refer to the American Journal of Hematology ^[2] (abstract).