Determinants of renal recovery and survival in patients with myeloma presenting with high circulating free light chains and renal impairement Free

Patients with significantly elevated involved free light chains (iFLC) in myeloma have a high risk of renal impairment (RI) and aggressive disease. This study was performed to describe patterns and determinants of renal recovery and survival in this patient subset.

All patients diagnosed with myeloma between January 2023 and 2025, with baseline iFLC greater than 1000 mg/L were included. Glomerular filtration rate (GFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and RI was defined as eGFR<60 mL/min/1.73m². Treatment and renal responses were assessed as per International Myeloma Working Group (IMWG) criteria. Progression free survival (PFS) was defined as time from diagnosis to progression or death. Multivariable logistic regression and Cox proportional hazards models were used to identify predictors of renal and survival outcomes. Light chain levels were log-transformed to account for data skewness.

A total of 122 patients with a median age of 63 years (IQR 55–69) and M:F ratio of 69:53 were included. Median baseline biochemical values were: kappa 198 mg/L (IQR 28–4068), lambda 53 mg/L (IQR 15–1897), iFLC 2868 mg/L (IQR 1000–7373), creatinine 2 mg/dL (IQR 1.01–6.93), and eGFR 47 mL/min/1.73m² (IQR 9–89). RI was present in 71 (58%) patients at baseline, who had a significantly higher iFLC (6064 vs. 1280 mg/L, p=0.000) and creatinine (5.65 vs. 0.9 mg/dL, p=0.000) compared to the remaining cohort. Hemodialysis was required in 12 (9.8%) and plasmapheresis in 6 (4.9%) patients. Those receiving plasmapheresis had lower baseline eGFR (Median 7.42, IQR 3.2–10.64, p=0.02) and higher iFLC (Median 10,799, IQR 9382–57,352) compared to the remaining cohort. Initial treatment regimens included bortezomib, cyclophosphamide, dexamethasone (VCD) in 66 (54.1%), bortezomib, lenalidomide, dexamethasone (VRD) in 34 (27.9%), daratumumab-based quadruplets in 6 (4.9%), and other combinations/doublets in 16 (13.1%) patients.

At first reassessment (median 90 days, IQR 36–124), median value of iFLC was 6.32 mg/L (IQR 1.66–27.1), creatinine 1.11 mg/dL (IQR 0.8–2.96), and eGFR 68.5 mL/min/1.73m² (IQR 22.4–113.5). Among those with baseline RI, the median change in creatinine was –1.7 mg/dL (IQR –5.27 to –0.55) and eGFR was +14.8 mL/min (IQR 5.3–31.4), though repeat eGFR remained lower compared to those without RI (Median 31.25 vs. 111.79, p=0.0000). IMWG renal responses (n=58 evaluable patients) included complete response in 6 (10.3%), partial in 11 (18.9%), minimal in 10 (17.2%), and no response in 31 (53.4%). Higher baseline creatinine showed a statistically non-significant trend toward reduced odds of renal recovery (OR 0.71, 95% CI: 0.34–1.01) and was strongly correlated with creatinine at last follow-up (Spearman's ρ = 0.69; p < 0.0001).

Myeloma status at reassessment (n=88 evaluable) was VGPR in 55 (62.5%), VGPR with normalized FLC ratio (VGPRn) in 29 (32.9%), PR in 3 (3.4%), and progressive disease in 1 (1.1%). Higher odds of achieving VGPR/VGPRn was observed in patients with a higher baseline eGFR (OR 0.97, 95% CI: 0.94–0.99, p=0.010).

At a median follow-up of 10.2 months (IQR 5.7–14.8; range 0–47.4), 80 (65%) were alive and in remission (PR or better). Seventeen (13.9%) patients died, 10 (8.1%) were alive with PD, and 15 (12.2%) were lost to follow-up. Median PFS was 16.3 months (95% CI: 15.1–29.9), with 12-, 24-, and 36-month PFS rates of 71.8%, 36.9%, and 7.4%, respectively. Median OS was 29.9 months (95% CI: 17.3–NR), with 12-, 24-, and 36-month OS rates of 88.9%, 63.9%, and 19.2%. On univariate Cox regression, higher baseline creatinine was associated with inferior OS (HR 3.28, 95% CI: 1.41–7.64, p=0.0058), and higher baseline eGFR was predictive of improved OS (HR 0.97, 95% CI: 0.94–0.996, p=0.025). There was no effect of age or baseline iFLC values on survival.

In our cohort, renal impairment (RI) was present in 58% and strongly associated with higher baseline iFLC and creatinine. Despite significant biochemical improvements, complete renal recovery was limited (10.3%), with over half showing no renal response. Higher baseline eGFR predicted deeper disease responses (VGPR/VGPRn) and improved overall survival, which was independent of age or extent of iFLC elevation. Median PFS (16.3 months) and OS (29.9 months) were suboptimal, highlighting the need for early, aggressive therapy in myeloma with RI to improve renal and survival outcomes.