A Multi-Center Analysis of Renal Impairment as a Potential Prognostic Factor: Analysis in Multiple Myeloma Patients Treated with Standard or High-Dose Chemotherapy Followed by Autologous Peripheral Blood Stem Cell Transplantation.
Authors: Kleber Martina , Ihorst Gabriele , Jakob Christian , Liebisch Peter , Koch Bernd , Engelhardt Monika 
Published: October 2019

Abstract
Renal impairment (RI) of varying severity including end stage renal disease is a common manifestation of multiple myeloma (MM). Nevertheless, the influence of milder - and via creatinine (crea) determination invisible - RI as a risk factor in MM patients (pts) is less well defined. We have previously reported in 167 cancer pts that estimating the glomerular filtration rate (eGFR) as compared to serum crea- or cystatin-levels determines prognostically adverse risk groups (Ann Oncol18: 950–8, 2007). In order to analyze the frequency of RI stages in a homogenous pt group, we determined RI in 198 consecutive MM pts receiving standard (Std; n=103) or high-dose chemotherapy (hd-CTx; n=95) in a multi-center study. We analyzed disease-stage, sex, age, performance status, β2-microglobulin, serum crea and GFR calculated by both the four-component “Modification of Diet in Renal Disease” (MDRD) and Cockcroft-Gault (CG). Evaluated outcomes were overall survival (OS) and progression free survival (PFS). Of note, although median crea, MDRD- and CG-eGFR-values appeared almost normal with 0.9mg/dl, 87 and 82ml/min/1.73m2, respectively, RI as determined as advanced chronic kidney disease (CKD stage >3 = eGFR<60) was apparent in 25% of all pts. We also observed distinct differences in pts receiving Std vs. hd-CTx: the median age was higher with 67 years (y) in the Std vs. 57y in the hd-CTx group (p<0.05). Advanced disease, as defined as number of pts with Durie & Salmon stage II/III, was comparable in both groups (92 vs. 97%, respectively). Although the crea was still within normal ranges in the Std- (1mg/dl) vs. hd-CTx-pts (0.8mg/dl), MDRD- and CG-formulas uncovered relevant differences between both groups: both MDRD- and CG-eGFRs being significantly decreased in Std- vs. hd-CTx-pts (MDRD: 72 vs. 96; CG: 68 vs. 101, respectively; p<0.05). Correspondingly, more Std-pts showed a decreased eGFR <60 than hd-CTx-pts (34 vs. 14%). Comparing solely those Std vs. hd-CTx-pts with active, progressing and/or proliferating myeloma also ascertained significant eGFR-differences in terms of decreased MDRD- and CG-levels, as well as more pts with CKD stage 3–5 in the Std group. This suggests that these MM pts had a significantly different renal function in Std-pts, most reliably, however, only detected via eGFR and CKD staging assessment, rather than the serum crea alone. Associated with RI (eGFR <60), PFS and OS were significantly decreased as compared to eGFR values >60 with estimated median values of 15 vs. 20 months and 36 vs. 61.3 months, respectively (p<0.05). In line, PFS and OS for Std- and hd-CTx-pts for eGFR<60 were considerably lower as compared to pts with eGFRs>60. In conclusion, we highlight the importance of efficiently detecting RI by means of eGFR-assessment, which allows to detect MM pts with mild - and/or via crea determination invisible - RI. Our data demonstrate that eGFR-decline substantially diminishes PFS and OS in consecutive MM pts, and suggest that with RI, Std- as opposed to hd-therapies do not substantially improve PFS/OS, so that novel therapy approaches are especially needed for those pts with RI, not receiving hd-CTx. These findings should also hold true for other cancer pts.