Thalidomide versus dexamethasone for the treatment of relapsed and/or refractory multiple myeloma: results from OPTIMUM, a randomized trial.
Author(s): Kropff M, Giongco-Baylon H, Hillengass J, Robak T, Hajek R, Liebisch P, Goranov S, Hulin C, Blade J, Caravita T, Avet-Loiseau H, Moehler TM, Pattou C, Lucy L, Kueenburg E, Glasmacher A, Zerbib R, Facon T
Publication date & source: 2011-12-01, Haematologica., [Epub ahead of print]
Background. Thalidomide has potent antimyeloma activity, but no prospective randomized controlled trial has evaluated thalidomide monotherapy in patients with relapsed/refractory multiple myeloma. Design and Methods. We conducted an international, randomized, open-label, 4-arm, phase III trial to compare 3 different doses of thalidomide (100-, 200-, or 400-mg/day) with standard dexamethasone in patients who had received 1-3 prior therapies. The primary endpoint was time-to-progression. Results. In the intent-to-treat population (N=499), median time-to-progression was 6.1, 7.0, 7.6, and 9.1 months in patients treated with dexamethasone, and thalidomide 100-, 200-, and 400-mg/day, respectively; the difference between treatment groups was not statistically significant. In the per-protocol population (n=465), median time-to-progression was 6.0, 7.0, 8.0, and 9.1 months, respectively. In patients who had received 2-3 prior therapies, thalidomide significantly prolonged time-to-progression at all dose levels versus dexamethasone. Response rates and median survival were similar in all treatment groups, but the median duration of response was significantly higher in all thalidomide groups versus dexamethasone. Adverse events reported in the thalidomide groups, such as fatigue, constipation and neuropathy, confirmed the known safety profile of thalidomide. Conclusions. This was the first randomized controlled trial to Although thalidomide was not superior to dexamethasone in this randomized trial, demonstrate that thalidomide monotherapy may be considered is an effective salvage therapy option for relapsed/refractory multiple myeloma, particularly in patients with good prognosis and those who have received 2-3 prior therapies. The recommended starting dose of thalidomide monotherapy is 400 mg/day, which can be rapidly reduced for patients who cannot tolerate treatment.(Clinical trial registration number: NCT00452569).