El-Husseiny, Khaled M.

e19543 Background: Multiple myeloma (MM) is a plasma cell malignancy characterized by immune dysfunction and end-organ damage. Emerging preclinical evidence suggests vitamin D is implicated in MM biology through effects on plasma cell differentiation and immune regulation. Vitamin D deficiency is common among patients with MM, yet its prognostic significance remains unclear. Clarifying its role may inform risk stratification and supportive management in MM. Methods: We conducted a retrospective cohort study using the multicenter TriNetX research network. Adults aged ≥20 years diagnosed with MM between 2011 and 2024 were included. Vitamin D status was defined using serum 25-hydroxyvitamin D levels, with deficiency defined as ≤30 ng/mL and normal levels defined as 31–80 ng/mL. Patients were stratified into two groups based on vitamin D status at the time of MM diagnosis. Propensity score matching (1:1) was performed to balance age, sex, race, baseline laboratory values, and clinically relevant comorbidities between groups. Kaplan–Meier survival analyses and Cox proportional hazards models were performed for outcome analyses. Results: A total of 36,273 patients with MM were included, of whom 42% (n = 15,262) had vitamin D deficiency. After propensity score matching, 14,023 vitamin D–deficient patients were well balanced with 14,006 non-deficient patients across baseline characteristics. In the matched cohort, the mean age was 64 years, 49% were female, and 64% were White. At five years, vitamin D deficiency was associated with a significantly higher risk of mortality (hazard ratio [HR] 1.63, 95% CI 1.54–1.72), with lower five-year overall survival (OS) compared with non-deficient patients (71.1% vs 80.8%, p<0.05). Vitamin D deficiency was also associated with increased risks of pneumonia (risk ratio [RR] 1.11), bacteremia (RR 1.22), and critical care admission (RR 1.30) (all p<0.05). Additionally, deficient patients had higher risks of acute kidney injury (AKI) (RR 1.19) and venous thromboembolism (RR 1.18) (both p<0.05). Notably, the risk of MM relapse was modestly increased among vitamin D-deficient patients (RR 1.07, 95% CI 1.01–1.13). No significant associations were observed between vitamin D deficiency and amyloidosis or pathologic fractures. In multivariable Cox regression, vitamin D deficiency remained independently associated with worse five-year OS (adjusted HR 1.60, 95% CI 1.52–1.67). Conclusions: This study highlights the negative impact of vitamin D deficiency in patients with MM. It identifies a high-risk subgroup of patients characterized by worse five-year OS, higher rates of serious infections, AKI, critical care utilization, and an increased risk of MM relapse. These findings suggest vitamin D deficiency as a clinically relevant prognostic marker in MM. Prospective studies are warranted to determine whether vitamin D level optimization can improve MM outcomes.

e19536 Background: Chronic kidney disease (CKD) may impair physiologic resilience during chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma (MM). While cytokine response syndrome (CRS) and immune cell-associated neurotoxicity syndromes (ICANS) have been described in MM CAR-T recipients with CKD, the broader cardiopulmonary, infectious, renal, and economic implications of CKD remain insufficiently defined. We examined the national impact of CKD on mortality, immune cell effector toxicities, organ dysfunction, infections and resource utilization. Methods: Adult MM hospitalizations receiving CAR T-cell therapy were identified from the National Inpatient Sample (2018–2022) using ICD-10-PCS codes. Patients with ESRD were excluded. CKD was categorized as CKD3a+ (eGFR <60 mL/min) versus no CKD/CKD1–2. Outcomes included in-hospital mortality, CRS (2021–2022), ICANS (2022), cardiac arrhythmias, acute kidney injury (AKI), renal replacement therapy, respiratory failure, infections and total hospitalization cost (calculated using TOTCHG variable and adjusted cost to charge ratio). Comparative analysis was done using chi-square testing. Multivariate analysis adjusted for demographics, comorbidities, and hospital characteristics. Results: Among 2,045 weighted MM CAR-T hospitalizations, 7.6% had CKD3a+. Overall CRS rates were similar (66.7% vs 64.9%; p=0.839) between CKD3a+ vs no/CKD1-2. Overall ICANS rates were also comparable (16.7% vs 17.3%; p=0.941). Differences in CRS/ICANS grades were not significant. CKD3a+ patients experienced sharply higher AKI (58.1% vs 13.0%; p<0.001; adjusted odds ratio [OR] 9.2, p<0.001). Renal replacement therapy was more frequent in CKD3a+ but non-significant (3.2% vs 0.8%; p=0.196). Acute respiratory failure was more frequent (9.7% vs 2.9%; p=0.045) in patients with CKD. Cardiac arrhythmias were numerically higher but non-significant (25.8% vs 20.6%; p=0.527; adjusted OR 1.3, 95% CI 0.4–4.9; p=0.673). Infections were amplified, including gram-negative bacteremia (3.2% vs 0.3%; p=0.026), sepsis (9.7% vs 2.6%; p=0.040), and septic shock (3.2% vs 0.3%; p=0.027) in patients with CKD. Inpatient mortality was numerically higher (6.5% vs 1.9%; p=0.101), though nonsignificant after adjustment (OR 6.9; p=0.319). Hospital costs were substantially higher in CKD3a+ (USD 346,769 vs 239,175; p=0.006), though not significant in adjusted models (OR 1.3; p=0.120). Conclusions: CKD3a+ is associated with markedly increased AKI, higher respiratory failure and infections, with a trend towards higher hospitalization costs. Inpatient mortality, CRS and ICANS rates were similar. CKD3a+ represents a significant vulnerability that amplifies downstream complications in MM CAR-T recipients, warranting enhanced pre-treatment risk stratification, infection surveillance and renal-preserving strategies.

Objective To quantitatively examine immune cell markers and spatial distribution in human diabetic kidney disease (DKD) to enhance understanding of the inflammatory landscape contributing to injury. Maladaptive inflammation is an underrecognized contributor to DKD pathogenesis and progression and remains undertreated. Patients and methods NanoString GeoMx™ Digital Spatial Profiling technology targeted antibodies labeled with unique oligonucleotide barcode in kidney biopsy [DKD (n=5), tubulointerstitial nephritis (TIN; n=4), and normal (n=2)] with regions of interest selection of compartments (glomeruli, tubules, interstitium). Inflammation-related proteins were analyzed with differential expression through linear mixed modeling. Results Compared to normal tissue, inflammatory cell surface protein markers were increased in DKD tubules and interstitium. Markers of T cells (CD4, CD44), macrophages (CD68; proinflammatory), and antigen-presenting cells (APCs; CD40 and CD11c) were increased across all DKD compartments (vs. normal). Macrophage (CD163; prorepair) marker was increased in DKD tubules and interstitium (vs. normal). Fewer differences were observed in glomeruli for normal vs. DKD or TIN vs. DKD groups. CD66b+ (granulocytes) cell marker was higher in DKD (vs. TIN). As expected, TIN had higher levels of T cell and macrophage markers in tubules and interstitium (vs. DKD). Interestingly, CD34, a hematopoietic stem cell and endothelial cell marker, was lower in DKD tubules and interstitium (vs. normal) but higher in DKD (vs. TIN). Conclusion NanoString GeoMx DSP technology may fulfil a role in enhancing the understanding the inflammatory landscape engaged in DKD pathogenesis as well as measuring response to therapy. Moreover, additional investigations of CD34 progenitor cell depletion in DKD may be warranted.