Renal impairment (RI) is a common complication of multiple myeloma (MM) that contributes to its morbidity and mortality. Previous studies have shown that early reduction of serum-free light chains (FLC) is associated with renal recovery. Some patients, however, developed irreversible RI, although they received novel agents and achieved early reduction of FLC. In the era of novel agents, the other factors of RI reversibility remain unclear.
The purpose of this study was to extend and update our previous research and determine the clinical variables that affect renal recovery in patients with RI who receive novel agents.
We retrospectively analyzed the medical records of patients with newly diagnosed MM with concurrent RI at the Kameda Medical Center (Chiba, Japan) between January 2008 and December 2018. RI was defined as an estimated glomerular filtration rate (eGFR) <50 ml/min per 1.73m2 that was measured before treatment by the simplified Modification of Diet in Renal Disease formula. Maximum renal response was evaluated according to the International Myeloma Working Group criteria. We defined major renal response as the achievement of CRrenal and PRrenal.
A total of 110 patients with RI and median age of 72 years, were included in this study; 56 (50.9%) achieved major renal response, including PRrenal (4.5%) and CRrenal (46.4%). There were significant differences in median percentage of urinary albumin and serum erythropoietin levels between the patients with and without major renal response, but the baseline involved FLC (iFLC) and percentage of iFLC reduction at day 12 and 21 was not significantly different. As the level of circulating erythropoietin is increased by the presence of anemia, 6 patients who did not have anemia (male, Hb < 12.0 g/dl; female, Hb < 11.0 g/dl) were excluded from the analysis associated with erythropoietin. The baseline of erythropoietin > 25 mIU/ml was associated with shorter time to rapid major response (2.4 months vs not estimated [NE] for erythropoietin ≤ 25 mIU/ml, P <0.001). Percentage of urinary albumin excretion was also associated with more rapid major response (3.0 months vs NE for percentage of urinary albumin > 25%, P < 0.001). Reduction of iFLC on days 12 and 21 tended to be associated with shorter time to major renal response, but the relation was not statistically significant. When we adjusted for age, baseline serum calcium, and baseline eGFR by multivariate analysis, erythropoietin > 25 mIU/ml (hazard ratio [HR], 5.99; 95% CI, 2.38–15.1; P < 0.001) and percentage of urinary albumin excretion ≤ 25% (HR, 6.67; 95% CI, 1.91–23.3; P = 0.003) were independent predictive factors for shorter time to major renal response.
We assigned a score of 1 to each of the two predictive variables (erythropoietin > 25 mIU/ml and percentage of urinary albumin excretion ≤ 25%). The median time to major renal response of patients with scores of 2, 1, and 0 points differed significantly (2.0 months vs NE vs NE, P < 0.001). The estimated rates of major renal response at 6 months of patients with scores of 2, 1, and 0 points were 78.6%, 30.6%, and 0%, respectively (Figure)
Our analysis, for the first time, indicated that the level of erythropoietin > 25 mIU/ml showed an independent positive predictive value for shorter time to major renal response. When the level of erythropoietin > 25 mIU/ml was combined with a percentage of urinary albumin excretion ≤ 25%, renal reversibility was predicted more accurately and patients with irreversible renal impairment could be detected.