Improved Outcomes of Myeloma Cast Nephropathy in Newly Diagnosed Multiple Myeloma With Modern Anti‐Myeloma Therapies

ABSTRACT Myeloma cast nephropathy (MCN) is a driver of renal failure in newly diagnosed multiple myeloma (NDMM) and has been historically associated with increased early mortality. Since patients with moderate to severe renal insufficiency are typically excluded from trials, we performed a retrospective study to characterize modern‐era outcomes in MCN. We reviewed 274 consecutive NDMM patients from 2017 to 2023 at an academic center and identified 46 patients (16.8%) with MCN. Among them, 96% had received bortezomib and 67% anti‐CD38 + monoclonal antibody in frontline therapy. As per the International Myeloma Working Group criteria, the renal overall response rate was 76.1% (35/46), and the renal complete response (CR) rate was 32.6% (15/46) at 6 months. Overall survival (OS) at 6 months did not differ between MCN (100%) and controls (98.2%). At a median follow‐up of ~3 years, the mean MCN OS was within 7 months of control ( p  = 0.039) by equivalence testing. Most involved free light chain (iFLC) and proteinuria reduction occurred within 1 month of treatment (83.1%, 3.9 g/d, respectively). In summary, we report excellent 6‐month renal recovery without early mortality in MCN patients with modern anti‐myeloma therapies. Prospective studies focused on MCN are urgently needed to further improve the renal CR rate.