Rapid Reduction of Light-Chains and Proteinuria in Multiple Myeloma (MM) Patients with Light Chain Induced Acute Renal Failure Treated with Lenalidomide and Dexamethasone

• Published in: Blood 2011-11, Vol.118 (21), p.5114-5114
• Main Authors: Ludwig, Heinz, Thaler, Josef, Koren, Jan, Pour, Ludek, Müldür, Ercan, Schreder, Martin, Zojer, Niklas, Weissmann, Adalbert, Adam, Zdenek
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V118.21.5114.5114

Abstract 5114 Light chain-induced renal failure (LC-ARF) is a severe complication of MM associated with increased risk of infections, dependency on chronic hemodialysis and shortened survival. Reversibility of renal impairment depends on the degree of renal damage, the duration of renal failure and the quality of response to anti-myeloma therapy. In this phase II trial we assess the efficacy of lenalidomide-dexamethasone in reducing pathogenic light chains and restoring renal function. In addition, we analyze the kinetics of treatment response in patients with LC-ARF. Patients and Methods: 24 patients with LC-ARF as formerly defined (JCO 2010) have been enrolled so far. Age (median): 65.5 years (range: 46–78 years), Gender: male/female: 12/12. All patients presented with ISS stage III. 20 (83.3%) had de novo MM and 4 (16.7%) previously treated, but relapsing disease. Median GFR was 19.9 ml/min (range 6.1 – 37.2 ml/min). ECOG performance was 0 in 6, I-II in 14 and III-IV in 4 patients, respectively. One patient died before first study medication, 3 patients died within the first cycle and 2 patients dropped out early (< 2 cycles). Lenalidomide was given from d 1–21 with dose adaptation according to GFR. Dexamethasone 40 mg was administered on d 1–4, 9–12, 17–20 during cycle 1; thereafter 1x/week. Cycles were repeated q 4 weeks. Presently, 17 patients are evaluable for response (completed ≥2 cycles and fully documented). The median number of cycles is 9 (range 2–9). CR was achieved in 5 (31.3%), nCR in 4 (25%), VGPR in 2 (12.5%) and PR in 5 (25%) patients, respectively, yielding an ORR (CR+nCR+VGPR+PR) of 94% for the evaluable and 69.6% for the ITT population. Median time to best tumor response was 132 days. The greatest proportional reduction in 24 hour urinary excretion (86%) in responding patients occurred within the first 4 weeks of therapy, with only little further improvement beyond that time (figure 1). Renal response was assessed as formerly defined (JCO 2010). 3 patients achieved CRrenal, 3 PRrenal and 5 MRrenal, yielding an ORRrenal in 11 patients (64.7% of the evaluable and 47.8% of the ITT population). Median time to best renal response was 83 days. 3 of 10 dialysis dependent patients became dialysis independent. Median GFR of evaluable patients increased from 15.2 (range 6.1 – 35.1 ml/min) at baseline to a median best GFR of 28.3 ml/min (range 11.3 – 101.1 ml/min) (p