ATLANTAPatients with relapsed or refractory multiple myeloma have a higher response rate and longer time to progression when lenalidomide (Revlimid) is added to dexamethasone(Drug information on dexamethasone) (Len/Dex), regardless of prior thalidomide(Drug information on thalidomide) (Thalomid). However, the benefit of the combination is greater in thalidomide-native patients, Michael Wang, MD, of M.D. Anderson Cancer Center, said at the American Society of Clinical Oncology 2006 Annual Meeting (abstract 7522).
The investigators analyzed data from two randomized, double-blind, placebo-controlled phase III trials in relapsed or refractory multiple myeloma (MM009 and MM010) that pitted Len/Dex against Dex alone. Analyses were based on 346 patients in each treatment group: 39% of patients had previously received thalidomide. Compared with their thalidomide-nave counterparts, thalidomide-exposed patients had received significantly more prior lines of therapy (median, three vs two) and were enrolled a significantly longer time after their diagnosis (median, 4.0-4.3 years vs 2.8-2.9 years).
The overall rate of response was significantly greater with Len/Dex than with Dex alone, both among patients who had received thalidomide previously (53% vs 15%) and those who had not (63% vs 28%). However, the rate with the combination was significantly higher in the thalidomide-nave group (63% vs 53%). "Since the partial response rate is equally 45%, the difference was accounted for by the difference in the complete response rate," Dr. Wang noted.
The median time to progression was significantly longer with Len/Dex than with Dex alone, both among thalidomide-exposed patients (8.5 vs 4.6 months) and thalidomide-nave patients (14.2 vs 4.7 months). Similarly, median overall survival was significantly longer with the combination whether patients had been treated with thalidomide before (not reached vs 17.9 months) or not (29.6 vs 23.5 months).
Compared with Dex alone, Len/Dex was associated with a higher rate of deep vein thrombosis and pulmonary embolism among patients with prior thalidomide (18% vs 3%). "Curiously, that was not true in the no-prior-thalidomide group," Dr. Wang said, but there was a modest incidence of thromboembolic events with Len/Dex in that group as well (12% vs 7%). "Thus, antithrombotic agents such as aspirin(Drug information on aspirin) appear justified," he said.
The greater efficacy of Len/Dex in thalidomide-nave patients relative to their thalidomide-exposed counterparts "may be explained by the fact that the thalidomide-exposed patients received heavier prior treatment and were later in their disease course," Dr. Wang concluded. "Whether this is due to thalidomide-induced resistance is currently unknown, and it remains the most important next step of this ongoing analysis."