P-174: Outcomes of Patients with Newly Diagnosed Myeloma Cast Nephropathy in the Modern Era-A Retrospective Cohort Study

Introduction: Myeloma cast nephropathy (MCN), caused by the precipitation of immunoglobulin light chain in renal tubules, is a negative prognostic biomarker in newly diagnosed multiple myeloma (NDMM). Trials often exclude patients with moderate-severe renal failure and do not uniformly report International Myeloma Working Group (IMWG) criteria-based renal response. Thus, the outcomes of MCN patients are not well-defined in the modern era, especially in those receiving anti-CD38 monoclonal antibody (anti-CD38mAb)-based frontline therapies. We retrospectively studied the MCN outcomes in the anti-CD38mAb era.

Methods: 274 consecutive NDMM patients were treated at CUIMC 11/15/18 to 4/01/24. MCN was defined as: no other causes of acute renal failure AND (a) evidence of light chain casts on renal biopsy; OR (b) serum creatinine of >2mg/dL, or 2021 CKD-EPI eGFR of < 40mL/min/1.73m2; ≥1g/d proteinuria; and involved FLC ≥50mg/dL. We used IMWG criteria to define renal response.

Results: 48 of 274 patients had MCN; 226 were contemporary controls. Median time from diagnosis to treatment in MCN patients was 6 days (IQR: 1-11.5 days). 36/48 MCN patients (75.0%) received upfront anti-CD38mAb-based regimens versus 121/226 (53.5%) controls.178/274 patients (65.0%) had an R2-ISS of at least 3 and 105/274 (38.3%) underwent autologous stem cell transplantation, without significant difference between MCN and controls. Baseline median eGFR (75.3 vs 18.5mL/min/1.73m²) and urine protein (0.336 vs 3.218g/d) were significantly increased in MCN patients vs controls (p < 0.001 for both). 68.2% of patients achieved at least a very good partial response by 6 months without significant difference between MCN and controls (p=0.344).



Of 7 MCN patients who required hemodialysis (HD) at diagnosis and survived 6 months, 3 (42.9%) became HD-independent at 6 months, and the remainder were HD-dependent. 6-month renal overall response rate was 72.9%, rate of partial response (PR) or better was 41.7%, and complete response (CR) rate was 37.5%. MCN patients receiving upfront anti-CD38mAb-based regimens had a numerically higher rate of renal PR or better versus those who did not (46.9% vs 37.5%, p=0.425). Median follow-up time was 31.0 months (range 0.8-133.2 months) for controls and 29.4 months (range 4.2-78.1 months) for MCN patients. Overall survival (OS) at 1 and 3 years was 94.4% (87.3-100%) and 73.3% (53.4-100%), respectively, in MCN patients receiving upfront anti-CD38 mAb; and 95.4% (92.2-98.8%) and 84.9% (77.8-92.7%), respectively, in controls (p=0.500). MCN patients receiving upfront anti-CD38 mAb had mean OS within 5 months of control OS (p=0.035).

Conclusions: MCN outcomes have improved in the modern era: >50% achieved renal response by 6 months and >33% achieved renal CR. There was no significant difference in early mortality between patients with or without MCN at diagnosis. Long-term follow-up is needed to determine if modern therapies can eliminate the negative prognostic impact of MCN.