Lenalidomide Is Effective Treating Patients With Relapsed Multiple Myeloma and Very Severe Renal Impairment

Introduction Patients with multiple myeloma (MM) and severe renal impairment (SRI) have shorter survival and are often excluded from clinical trials. In these patients the use of Lenalidomide (Len) is based in pharmacokinetic models and because of the risk of increased toxicity, Len dose must be adjusted to renal function. Purpose To evaluate the outcomes of relapsed MM patients (RMM) with SRI (baseline creatinine clearance (CrCl) <30ml/min) treated with Lenalidomide-dexamethasone (Lendex), including patients under hemodyalisis. Methods We conducted a retrospective multicenter study in four Portuguese referral hospitals. All consecutive patients with RMM and SRI treated with Lendex between January 2007 and December 2012 were included. Lendex treatment was considered as the administration of low doses of dexamethasone and Len doses between 25mg/d and 5mg every other day. We evaluated the efficacy (response rate (RR), response duration and impact on renal function) and the relevant toxicities (myelo and neurotoxicity, thrombotic and infectious complications and second primary tumors). Results We retrospectively analyzed 22 patients with SRI and RMM treated with Lendex (median CrCl at start of Lendex was 19 ml/min with 13 patients under dialysis): 55% males; median age at diagnosis 63yo; median age at start of Lendex 68yo (51-79); main subtypes were IgGk (45%) and IgGλ (18%); 3 patients with high-risk cytogenetics; 5 plasmocytomas; 1 amyloidosis; 77% received Lenalidomide ≤10mg/d x 21 days in monthly cycles; median 8 cycles (2-50). Median number of previous lines was 2 (1-6). The global RR was 72% (16/22; 12 patients with ≥PR); 6 pts had progressive disease. Five out of 6 (83%) of the patients who progressed with Lendex had prior exposure to thalidomide. Median follow-up from start of Lendex was 14 months (2 – 62). The median time until maximal response was 3 months and the median response duration was 31 months (5 – 55) and in 58% (7/12) the response was longer than 2 years. Eighteen percent had renal improvement (median CrCl improvement of 44ml/min) but all the 13 patients on hemodyalisis maintained the need for this treatment. The treatment was interrupted in 3 cases because of adverse events and all the patients were on thromboprophylaxis with aspirin. In the long-term responders a continuous Len dose adjustment was required mainly because of myelo and neurotoxicity and the dexamethasone dose was reduced according to toxicities (metabolic, fatigue and psychiatric effects). There were no critical infections or second primary tumors. Conclusions CrCl<60 ml/min is a cut-off for Lenalidomide dose reduction. In our experience, after initial dose-adjustment of therapy, there should be a continuous process of dose-adjustment taking into account the individual tolerance, even without additional renal impairment. Lendex dosing adjusted according to CrCl does not negatively impact response or the rate of side effects. It may also have a potential to reverse RI and induce long duration of response. We concluded that Lendex is an effective and safe treatment regimen for relapsed MM patients with severe renal insufficiency. Disclosures: Joao: yassen: member of advisory board, member of advisory board Other; Celgene: member of advisory board, member of advisory board Other. Esteves:Celgene: member of advisory board, member of advisory board Other; Yassen: member of advisory board, member of advisory board Other.