Detection of Renal Impairment (RI) as One Specific Comorbidity Factor in Multiple Myeloma (MM) Patients: Multi-Center Study in 198 Consecutive Patients
Authors: Kleber Martina , Ihorst Gabriele , Deschler Barbara , Jakob Christian , Liebisch Peter , Koch Bernd , Sezer Orhan , Engelhardt Monika 
Published: April 2020

Abstract
Introduction: Multiple myeloma (MM) is a clonal disorder characterized by an accumulation of malignant bone marrow (BM) plasma cells, lytic bone lesions, myelosuppression and renal impairment (RI). Due to improved treatment options, overall survival (OS) and quality of life have substantially improved. Nevertheless, elderly and comorbid MM patients are often excluded from intensive therapies due to underlying diseases, and patient and/or physician bias. We have previously reported in 167 cancer patients that estimated glomerular filtration rates (eGFR)-rather than serum creatinine, creatinine clearance or cystatin C-best determine prognostically adverse risk groups. Due to these results, we favor eGFR rather than creatinine, creatinine clearance or cystatin for the assessment of RI in cancer patients.
Methods: We determined MM-specific prognostic factors, comorbidities (via Satariano index [SI]) and RI via eGFR (by Modification of Diet in Renal Disease [MDRD]) to ascertain their value on progression free survival (PFS) and OS.
Results: 198 consecutive MM patients showed a median age of 61 years (y; range 27–83) and low comorbidity index (SI: 1; range 0–6). 94% of patients had advanced MM (Durie & Salmon [D&S] stage II/III) and 16% had stage B disease (creatinine ≥2.0mg/dl). Via eGFR determination, however, much higher patient numbers had detectable mild to advanced RI, whereby 29% were in chronic kidney disease (CKD) stage 3–5 (eGFR&lt;60ml/min/1.73m2) and 58% in CKD stage 2–5 (eGFR&lt;90ml/min/1.73m2). Analysis of patient and MM characteristics within the CKD stages 1–5 (1=≥90, 2=89–60, 3=59–30, 4=29–15, 5=&lt;15) revealed that age, ISS, LDH, β2-MG and BM-infiltration substantially increased with higher CKD stage and that unfavorable risks were associated with RI, if reliably measured by eGFR. Univariate analysis ascertained hazard risks (HRs) for impaired PFS and OS which substantially increased with RI as determined via eGFR (Table 1). Of note, HRs with impaired eGFRs were higher than simple creatinine measurements, than β2-MG, age or SI. HRs were also increased in patients with advanced MM stage (II/III or B by D&S) and advanced age (&gt;59y), albeit age did not reveal highest HRs (Table 1).
Table 1. Univariate analysis of various prognostic factors on PFS and OS
PFS OS Variables on PFS/OS HR (95% CI) p value* HR (95% CI) p value* *chi-square-test Disease-stage II/III 3.6 (1.29–9.77) 0.0143 3.4 (0.84–14.13) 0.0869 Disease-stage B 1.8 (1.15–2.79) 0.0100 2.2 (1.24–3.76) 0.0068 Age (&gt;59 y) 1.9 (1.36–2.74) 0.0002 1.9 (1.19–3.07) 0.0071 eGFR (MDRD, ml/min/1.73m2) eGFR &lt;90 (CKD stage 2) 1.7 (1.22–2.42) 0.0016 1.3 (0.86–2.13) 0.1860 eGFR &lt;75 1.6 (1.17–2.30) 0.0041 1.2 (0.79–2.13) 0.3319 eGFR &lt;60 (CKD stage 3) 1.5 (1.07–2.24) 0.0190 1.8 (1.09–2.86) 0.0207 eGFR &lt;50 1.6 (1.06–2.36) 0.0226 2.3 (1.44–3.85) 0.0006 eGFR &lt;30 (CKD stage 4) 1.8 (1.11–2.93) 0.0179 2.9 (1.62–5.08) 0.0003 β2-MG (≥3.5mg/dl) 1.8 (1.19–2.60) 0.0040 1.8 (1.09–3.14) 0.0232 Satariano index (SI) (≥3) 1.3 (0.69–2.52) 0.3941 2.0 (0.93–4.49) 0.0745 Karnofsky-index (≥90%) 0.6 (0.43–0.84) 0.0032 0.6 (0.36–0.91) 0.0194
Conclusions: RI-when carefully assessed via eGFR-is frequent in MM and a valuable prognostic and comorbidity factor for diminished PFS/OS. Increased age was lesser a prognostic factor than RI via eGFR, advanced myeloma stage or SI, demonstrating that numerical age is to a smaller extend relevant and that MM-specific risk scores should be beneficial to guide individual MM treatment. Our results highlight the debate on comorbidity scores and treatment decision-tools in MM which have not yet moved into routine clinical practise. We are currently comparing various comorbidity-scores, including a self-defined MM-score, which will be presented at the meeting.