Renal Impairment Is Not An Independent Adverse Prognostic Factor In Multiple Myeloma Patients Who Are Treated Upfront with Novel Agent-Based Regimens
Authors: Dimopoulos Meletios A. , Kastritis Efstathios , Roussou Maria , Gavriatopoulou Maria , Migkou Magdalini , Gkotzamanidou Maria , Iakovaki Marina , Matsouka Charis , Mparmparousi Despina , Nikitas Nikitas , Gika Dimitra , Grapsa Irene , Psimenou Erasmia , Terpos Evangelos 
Published: October 2019

Abstract
Abstract 3033
The adverse prognosis of renal impairment in patients with multiple myeloma (MM) has been reported in several series. However, the prognostic impact of renal dysfunction on the survival of MM patients who are treated upfront with novel agents has not been clearly defined. To address this question we studied 180 consecutive patients who received upfront novel agent (thalidomide, bortezomib or lenalidomide)-based regimens, in a single center in Athens, Greece. Many of these patients had been included in clinical trials; however, several patients who were ineligible because of poor performance status, significant renal impairment or comorbidities were also treated with novel agent-based regimens. Thus, these patients are more representative of the general myeloma population. Renal function, estimated by the glomelural filtration rate (eGFR) was assessed using the simplified Modification of Diet in Renal Disease (MDRD) formula (eGFR in mL/min/1.73 m2 = 186 × (Serum Creatinine)−1.154 × (Age)−0.203 × (0.742 if female) × (1.212 if African-American). Patients were divided into 5 groups according to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) chronic kidney disease (CKD) classification. According to this classification, stage 1 includes patients with eGFR ≥90 ml/min, while stage 2 includes patients with eGFR between 60–89 ml/min, stage 3 with eGFR between 30–59 ml/min, stage 4 with eGFR between 15–29 ml/min and stage 5 includes patients with eGFR below 15 ml/min or patients who undergo dialysis. Eighty-five patients (47%) had stage 3–5 CKD and 95 (53%) had stage 1 or 2 CKD. One half of our patients (51%) were 70 years of age or older. Advanced age (p=0.001), anemia (p<0.001), low serum albumin (p=0.017), hypercalcemia (p<0.001), elevated beta2-microglobulin (p<0.001) and Bence Jones proteinuria >2 g/day (p<0.001) were associated with stage 3–5 CKD. The majority of patients with International Scoring System (ISS)-3 myeloma had advanced renal disease (stage 3–5 CKD in 76%) in comparison with ISS-2 (33%) or ISS-1 (10.5%) patients (p<0.001). Eighty-one percent of our patients received upfront an IMiD-based therapy, while 19% received bortezomib-based regimens. The dose of lenalidomide was adjusted according to renal function. The frequency of advanced CKD was similar among patients treated with IMiDs- or bortezomib-based regimens (47% vs. 48.5%, p=0.843). Response to primary treatment was similar between patients with stage 3–5 CKD and patients with stage 1 or 2 CKD (72.6% vs. 78.7%, respectively; p=0.343). In the univariate analysis, variables associated with worse survival were: stage 3–5 CKD (median survival 39 months vs. not reached in stage 1 or 2 CKD; p=0.001), age ≥70 years (p<0.001), anemia (p=0.005), hypercalcemia (p=0.012), ISS stage (p<0.001) and LDH ≥300 IU/L (p=0.007). However, in the multivariate analysis, the presence of renal dysfunction (stage 3–5 CKD) or the degree of renal dysfunction (evaluating each CKD stage separately) was not independently associated with survival. Age >70 years (p<0.001), corrected serum calcium ≥11.5 mg/dl (p=0.04) and elevated LDH ≥300 IU/L (p=0.001) were the only independent factors associated with worse survival. The same results were obtained when we assessed renal function as a continuous variable. We also evaluated the effect of CKD staging on the survival of patients within each ISS stage and we did not find any statistically significant correlation. We conclude that the presence °r the degree of renal dysfunction has no independent prognostic impact on the survival of multiple myeloma patients who are treated upfront with novel agent-based regimens.

Disclosures:
No relevant conflicts of interest to declare.