Study Shows Thalidomide Good Treatment Option for Patients with Relapsed Refractory Multiple Myeloma
Patients with relapsed refractory multiple myeloma (RRMM) treated with thalidomide showed longer disease control in terms of time-to-progression (TTP) and duration of response (DOR) compared with high-dose dexamethasone, according to data presented at the 51st Annual Meeting and Exposition of the American Society of Hematology in New Orleans.
The OPTIMUM trial reported on at the meeting was designed to compare the efficacy of single-agent thalidomide with high-dose dexamethasone in patients with RRMM and to determine the optimal dose. Patients with RRMM who had progressed after 1-3 lines of prior therapy were eligible for the multinational, randomized, open label phase III study.
The researchers randomized patients to either daily thalidomide 100mg, 200mg, or 400mg, or dexamethasone (40mg daily on days 1-4, 9-12, and 17-20 of each 28-day cycle for four cycles. From cycle five onwards, the dosing schedule was reduced to 40mg daily on days 1-4 of each cycle). All patients received study medication until disease progression or for a maximum of 12 cycles. The primary endpoint was TTP validated by an Independent Review Committee (IRC). Secondary endpoints included response rate, clinical benefit, survival, quality of life, and safety. Planned accrual was 496 patients in order to detect a significant difference of three months in median TTP between the arms with 82% power at a two-sided significance level of 0.05.
Between April 2006 and Feb 2008, 499 patients were randomized by 68 sites in 15 countries from Europe, Asia, and South Africa. The median age was 64 years (range 33-86); 73% had ISS stage I+II; 56.7% had received one prior therapy; 29.7% had received two prior therapies; and 12.8% had received three prior lines; 14.4% of patients had received prior bortezomib. Patients who had received prior thalidomide or lenalidomide were not included in this trial.
Based on IRC-confirmed disease progressions during the treatment phase of the study, median TTP in the thalidomide 400 and in the dexamethasone groups were 9.9 versus 6.0 months (hazard ratio, 0.64; P=0.017). Median TTP of the thalidomide 100 and thalidomide 200 arms were 6.7 and 7.3 months, respectively. IRC-validated complete and partial response rates according to EBMT criteria were 20.7% with thalidomide 100, 18.0% with thalidomide 200, 21.5% with thalidomide 400, and 24.6% with dexamethasone. However, duration of response (DOR) showed a clear benefit for patients responding to thalidomide in comparison to dexamethasone (median DOR in months: thalidomide 100, 12.7, P=0.046; thalidomide 200, 13.1, P=0.005; thalidomide 400, 11.6, P=0.016; dexamethasone, 6.5). There was no difference in one-year overall survival between the groups (80%, 83%, 82%, and 80% for thalidomide 100, thalidomide 200, thalidomide and dexamethasone, respectively). Sixty percent of patients treated with thalidomide 400 had at least one treatment emergent AE (TEAE) of grade 3 compared to 39.5% with dexamethasone. Patients treated with lower doses of thalidomide showed a more favorable safety profile.
The researchers concluded that thalidomide is a good treatment option that has a dose-dependent safety profile.