Proteinuria with preserved renal function (PPRF): A retrospective cohort study in newly diagnosed multiple myeloma.

e19559 Background: Myeloma cast nephropathy (MCN) is a negative prognostic marker in newly diagnosed multiple myeloma (NDMM). Patients with NDMM also present with proteinuria without renal dysfunction. Such proteinuria may impact outcomes in the anti-CD38 + monoclonal antibody (mAb) era. We report the clinical course of PPRF patients. Methods: 41 PPRF patients, 59 MCN, and 232 controls were diagnosed 5/01/16-12/31/24. PPRF was defined as proteinuria ≥1g/d and involved free light chain (iFLC) titer ≥50mg/dL. MCN was defined by biopsy, or as eGFR ≤45mL/min/1.73m 2 with PPRF proteinuria and iFLC. Controls did not meet these criteria. High-risk cytogenetic abnormalities (HRCA) were defined per society guidelines. We obtained retrospective data on clinical course. Results: Median PPRF creatinine was similar to controls; median PPRF iFLC and proteinuria were similar to MCN. HRCA, upfront anti-CD38 + mAb, ASCT, and IMWG response rates did not differ. Mean 1 month and 6 month PPRF EGFR were 66.7 and 93.7mL/min/1.73m 2 . No PPRF patient needed RRT at 6 months. PPRF iFLC and urine protein-creatinine (UPC) ratio decreased significantly over 1, 3, and 6 months: 71.9% and 47.2%; 89.9% and 73.5%; and 85.1% and 72.4%. MCN patients showed similar patterns. In 25 PPRF patients with upfront anti-CD38 + mAb, mean iFLC and UPC reductions at 1, 3, and 6 months were: 81.2% and 67.7%; 92.1% and 72.4%; and 89.8% and 75.9%. Median study follow-up was 33.6 months (CI 29.6-36.5). 6 PPRF patients died: 3 of progression, 2 of infections, and 1 of FTT. 1 year disease-free and overall survival (DFS, OS) were: 92.5% PPRF, 94.9% MCN, and 96.8% control; and 88.8% PPRF, 98.3% MCN, and 99.1% control. DFS and OS did not differ (HR 0.97, CI 0.75-1.25, p = 0.797; HR 1.05, CI 0.71-1.53, p = 0.820). In patients with upfront anti-CD38 + mAb, 1 year DFS and OS were 81.9% PPRF, 86.4% MCN, and 86.6% control; and 81.0% PPRF, 94.1% MCN, and 96.4% control. In these patients, PPRF was associated with increased mortality vs controls (HR 1.34, CI 1.03-1.73, p = 0.027). Conclusions: PPRF patients exhibit sustained EGFR, without RRT need at 6 months, with “MCN-like” iFLC and UPC patterns. Despite upfront anti-CD38 + mAb, 6 month UPC reduction was <80%. In this group, mortality was higher for PPRF vs controls. PPRF may denote aggressive disease not fully accounted for by cytogenetic analysis. Alternatively, PPRF not resolving after 6 months despite modern therapy may signify vulnerability to infections, influencing mortality. Further study is needed to elucidate the pathophysiology, prognostic significance, and optimal management of PPRF in this context. Selected features. PPRF MCN Controls p Baseline Cr (mg/dL) 1.14 (0.91-1.39) 3.18 (2.34-5.28) 1.01 (0.75-1.32) <0.001 Baseline urine protein (g/d) 2.01 (1.27-3.71) 3.30 (1.56-5.98) 0.21 (0.13-0.45) <0.001 1 st line anti-CD38 + mAb 58.5% 69.5% 56.0% 0.173 ASCT 43.6% 33.9% 34.5% 0.707 6 month ≥VGPR 70.2% 70.9% 82.3% 0.233