Estimation Of GFR With Different EGFR Equations In Multiple Myeloma Patients Receiving Lenalidomide Treatment

Abstract

IntroductionRenal impairment (RI) in patients with MM is detrimental organ damage. The estimation of glomerular filtration (eGFR) rates is based on using different equations such as CKD-EPI, MDRD or Cockcroft-Gault (CG). Methods: We enrolled 132 consecutive MM patients treated with lenalidomide for the approved indication in our department between 2006 and 2012. The GFR for quantifying RI was estimated by the CKD-EPI, MDRD- and CG-equations at baseline and after 3 months under lenalidomide therapy. We assessed hematological response by the EBMT criteria, and renal response according to recently proposed criteria (Dimopolous et al. Leukemia 2013) and by comparing the CKD-EPI, MDRD- and CG equations. ResultsMedian patient age was 64 years (range 41-90; males 62%) with predominantly advanced stage II/III Durie & Salmon and International Staging System disease (96% vs. 65%, respectively). Fifty-four MM patients had received ≥2 therapy lines and 50% prior stem cell transplantation. The median lenalidomide dose was 25mg (D1-21/28 day cycle) given with dexamethasone (Rd) as published. The median serum creatinine was normal at 1.0mg/dl, whereas the median eGFR showed CKD stage 2, with substantially different median CKD-EPI, MDRD and CG equations of 77, 81 and 74ml/min/1.73m2, respectively (Figure 1A). For each equation, the number of patients with CKD stage 3–5 via CKD-EPI, MDRD and CG equation was 32%, 23% and 30%, respectively (Table 1). In total, 26 (20%) MM patients with eGFR values by the MDRD equation were reclassified to higher CKD-stages according to CKD-EPI equation and 3 (2%) to lower CKD stages (Figure 1B). This demonstrates that the MDRD may substantially overestimate the GFR, especially in elderly patients with normal or less impaired renal function (GFR >60ml/min/1.73m2). Best overall response (ORR=CR+PR) and clinical benefit rate (CR, PR, SD) in this advanced, substantially pretreated cohort was 48% and 93%, respectively. After 3 months, renal response (CR, PR, MR) according to CKD-EPI, MDRD and CG were 17%, 11% and 15%, respectively, and renal response defined as any eGFR improvement was 52%, 51% and 51%, respectively. For each eGFR equation, the number of patients with renal improvement according to CKD stage 1-2 was more pronounced with the CKD-EPI (68% → 76%), less with the MDRD (77% → 83%) and least with the CG equation (70% → 75%; Table 1). [Display omitted] Table 1Estimated CKD stages and prevalence of CKD stages 3-5 by different eGFR equations at baseline and after 3 months lenalidomide therapyBaselineAfter 3 monthsBaselineAfter 3 monthsBaselineAfter 3 monthsVariablesCKD-EPIMDRDCockcroft-Gaultn (%)n (%)n (%)n (%)n (%)n (%)CKD stage (ml/min/1.73m²)1: eGFR ≥9035 (26)68%40 (33)76%46 (35)77%49 (41)83%49 (37)70%47 (39)75%2: eGFR 89-6055 (42)51 (43)56 (42)50 (42)43 (33)43 (36)3: eGFR 59-3033 (25)32%22 (18)24%21 (16)23%14 (12)17%32 (24)30%23 (19)25%4: eGFR 29-157 (5)6 (5)8 (6)7 (5)7 (5)5 (5)5: eGFR <152 (2)1 (1)1 (1)0 (0)1 (1)1 (1) ConclusionsTo the best of our knowledge, we are the first to demonstrate that measuring renal function by the CKD-EPI equation in Rd-treated MM patients is highly valuable. In these substantially pretreated MM patients, renal response under lenalidomide was seen via CKD-EPI in 17% and any eGFR improvements in 52%, indicating that Rd in these patients is effective and RI best defined via CKD-EPI. Our results enlarge the arsenal of available eGFR equations by the CKD-EPI formula. Disclosures:Kleber:Celgene: Educational grant Other. Engelhardt:Celgene: Educational grant Other.