The efficacy and safety of lenalidomide plus dexamethasone in relapsed or refractory multiple myeloma patients with impaired renal function

8542 Background: Renal impairment (RI) is common among patients (pts) presenting with myeloma (MM) and requires aggressive early intervention. Two recently published phase III trials showed significant benefit after treatment with lenalidomide plus dexamethasone (Len/Dex) over Dex alone for pts with refractory or relapsing MM. Methods: In pooled data, 682 pts with serum creatinine (Cr) ≤2.5 mg/dL received treatment at a starting dose of 25 mg/day Len on days 1–21 and 40 mg/day Dex on days 1–4, 9–12, and 17–20days 1–4, every 28-day cycle. We now evaluate efficacy and safety of Len/Dex and Dex alone in the subgroup of pts who had normal (CLcr >80 mL/min), mild (50≤ CLcr <80 mL/min), moderate (30≤ CLcr <50 mL/min), or severe (CLcr <30 mL/min) RI despite Cr ≤2.5mg/dL. Results: Len/Dex significantly improved time-to-progression and response rate compared with Dex for pts with normal to moderately impaired RI (Table; P<0.001); in severe RI TTP was significantly longer with Dex alone, but shorter than for pts without RI or with mild RI. At the starting doses for Len and Dex, the limited number of pts with CrCl < 30 mL/min had a higher percentage of myelosuppression compared with those with CrCl > 30 mL/min (Table). In pts treated with Len/Dex, 78% (42/54) of those with moderate to severe RI had improvement in renal function within 4 months of treatment. Conclusions: Pts with moderate or severe RI respond equally well to treatment with Len/Dex for relapsed or refractory MM. With careful monitoring of adverse events and appropriate dose adjustments, this study showed that a favorable outcome could be achieved with Len/Dex despite renal impairment. Prospective trials will define the activity and tolerability of Len/Dex in patients with RI. Treatment group CLcr < 30 mL/min P 30 ≤ CLcr < 50 mL/min P 50 ≤ CLcr < 80 mL/min P CLcr > 80 mL/min P Len/Dex (n=16) Dex (n=12) Len/Dex (n=42) Dex (n=34) Len/Dex (n=125) Dex (n=132) Len/Dex (n=158) Dex (n=163) Response rate, % ORR 50.0 25.0 0.205 61.9 20.6 0.001 64 19.8 <0.001 63.9 27.0 <0.001 CR 6.3 8.3 21.4 0.0 12.8 2.3 16.5 1.8 VGPR 31.3 0.0 11.9 0.0 21.6 2.3 13.9 4.3 PR 12.5 8.3 26.2 20.6 27.2 15.2 32.9 19.0 Efficacy, months Median TTP 7.9 4.7 0.031 11.4 2.8 <0.001 12.1 4.7 <0.001 11.3 4.7 <0.001 Overall survival 18.6 16.9 0.849 30.4 12.5 0.068 34.7 27.2 0.131 NR 101.2 0.142 Adverse events, % Neutropenia 37.5 8.3 0.184 42.9 5.9 <0.001 39.2 1.5 <0.001 31.0 4.3 <0.001 Thrombocytopenia 37.5 >0.0 0.024 19.0 17.6 1.00 16.0 5.3 0.007 7.0 5.5 0.649 Thrombotic episodes 6.3 8.3 1.00 14.3 2.9 0.122 12.0 6.1 0.126 11.4 1.8 <0.001 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene Celgene Celgene Celgene Celgene