The following table depicts the results from the FIRST trial (MM-020), excerpted from the product information of lenalidomide (Revlimid®).r Progression free survival was statistically superior compared to Rd18 and MPT arms; overall survival showed trend in favour of Continuous Rd but did not reach the threshold for significance.
In MM-009,r 177 patients were assigned to the lenalidomide/dexamethasone group and 176 to the dexamethasone group. Complete, near-complete, or partial responses occurred in 108 patients (61.0%) in the lenalidomide group and in 35 patients (19.9%) in the placebo group (P<0.001); complete responses occurred in 14.1% and 0.6%, respectively (P<0.001). The median time to progression was 11.1 months in the lenalidomide group and 4.7 months in the placebo group (P<0.001). Median overall survival times in the two groups were 29.6 months and 20.2 months, respectively (P<0.001). In MM-010,r 176 patients were assigned to the lenalidomide/dexamethasone group and 175 to the dexamethasone group. Complete, near-complete, or partial responses occurred in 106 patients (60.2%) in the lenalidomide group and in 42 patients (24%) in the placebo group (P<0.001); complete responses occurred in 15.9% and 3.4%, respectively (P<0.001). The median time to progression was 11.3 months in the lenalidomide group and 4.7 months in the placebo group (P<0.001). Overall survival was significantly improved in the lenalidomide group (hazard ratio for death, 0.66; P = 0.03). A pooled analysis with longer follow-up (median 48 months) confirmed lenalidomide/dexamethasone significantly improved overall response (60.6 vs. 21.9%, p<0.001), complete response rate (15.0 vs. 2.0%, p<0.001), time to progression (median 13.4 vs. 4.6 months, p<0.001), duration of response (median of 15.8 vs. 7 months, p<0.001), and overall survival (median 38.0 vs. 31.6 months, p=0.045).r A further analysis suggests this efficacy is maintained in patients aged over 65 years.r A small non randomised study of 45 patients aged over 75 years with relapsed myeloma found 62% overall response rate and median progression free survival of 14 months, similar to the MM-009 and MM-010 studies.r
Lastly most studies have utilised a high-dose dexamethasone regimen of 40 mg on days 1 to 4, 9 to 12 and 17-20 in the first four 28 days cycles with 40 mg on days 1 to 4 in subsequent cycles. Rajkumar et alr compared this high-dose dexamethasone regimen with 40 mg on days 1, 8, 15 and 22 of every 28 days cycle during the first 4 cycles in patients with newly diagnosed myeloma prior to ASCT. The study was stopped after the second interim analysis with 50% of patients completing the study and a median follow-up of 1 year as overall survival (a secondary endpoint) was significantly greater in the low-dose dexamethasone cohort (96% vs 87% overall survival, p=0·0002). Grade 3 or higher toxicity (52% vs 35% p=0.0001), deaths (12 vs 1, p=0.003), venous thromboembolism (26% vs 12% p=0.0003) and infection (16% vs 9% p=0.04) were significantly more frequent in the high-dose dexamethasone cohort. Given this and other experience with the high-dose dexamethasone regimens the reference committee recommend that the dexamethasone dose be individualised or dose reduced where the high dose regimen is not well tolerated (i.e. in older patients or those that develop severe steroid related side effects).
Response rates, TTP, PFS and OS: Pooled Analysis of MM-009 and MM-010 Trials:r
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