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Statistical analyses and sample size Target accrual was [You must be registered and logged in to see this link.] 194 patients, including 184 patients in the treatment cohort and 10 patients in the PK co hort. For the PK cohort, the target sample size was 10 patients, to obtain reasonable estimates of systemic ex posure to lenalidomide in patients with adequate renal function. For this analysis, the primary population in cluded the first 176 patients enrolled in the treatment cohort and the 11 patients enrolled in the PK cohort. The efficacy evaluable population included all patients who took 1 dose of the study drug, had meas urable disease at baseline, and had 1 post baseline re sponse assessment. To provide the most complete safety information, the safety population included all patients who had enrolled and received 1 dose of study drug before data cutoff.

The Kaplan Meier method was used to estimate the survival distribution function for PFS, response [You must be registered and logged in to see this link.] duration, and overall survival. The effect of dexamethasone on lenalidomide exposure at steady state was evaluated by comparing area under the plasma concentration time curve, AUC from time 0 to infinity, and maximum observed plasma concentration between Day 7 and Day 8, using an analysis of variance model with treatment as a fixed effect and pa tient as a random effect on the natural log transformed parameters. Results Patient disposition A total of 199 patients were enrolled in the study and were evaluable for safety. At the time of the final analysis, 42 patients continued to receive study treatment, 156 had discontinued, and 1 patient had com pleted treatment.

Treatment discontinuations were due to progressive disease, consent withdrawal, death, AEs, or protocol violation. The final efficacy analysis was based on the primary effi cacy population of 187 patients. The median treatment duration was 8. 3 months and the median number of cycles was 9. The median durations of lenalidomide [You must be registered and logged in to see this link.] and dexamethasone treatment were 7. 8 months and 7. 6 months, respectively. The median relative dose intensity was 1. 0 for both lenalidomide and dexamethasone, suggesting that most pa tients received their dose of study medication as planned over the course of the study. The proportion of patients receiving the 25, 20, 15, and 10 mg doses of lenalidomide over 12 progressive treatment cycles is shown in Figure 2. The majority of patients per treatment cycle remained on the 25 mg day starting dose.

Baseline demographics Patient characteristics at baseline are shown in Table 1. The median age of patients in the primary efficacy popu lation was 60. 0 years, 71. 1% were aged 65 years, and 62. 0% were male. Most patients in the primary population had advanced disease and were heavily pre treated, 56. 7% had received 4 prior regimens and most had received prior thalidomide, bortezomib, or both. In addition, 5. 4% of patients had the immunoglobulin D subtype of MM. Most patients had normal renal function, 26. 7% had mild to moderate impairment, and 6. 4% had severe impair ment. Baseline patient characteristics were comparable between the primary and the safety populations. Efficacy The primary efficacy endpoint of best ORR in the efficacy evaluable population was 47. 6%, including 23 patients with a VGPR and 7 pa tients who had a complete response.