Citations

7542 Background: Teclistamab, a novel bispecific monoclonal antibody targeting CD3 and BCMA, exhibits promising effects for patients with relapsed and refractory multiple myeloma (MM). However, rates of acute kidney injury (AKI) associated with this therapy remains inadequately characterized. Methods: This was a retrospective observational cohort study of patients with relapsed refractory MM who received teclistamab or Chimeric Antigen Receptor T-cell Therapy (CAR-T) therapy at Mayo Clinic between 12/1/2022-5/15/2023 and who were not in kidney failure at the time of treatment. The primary endpoint was incidence of AKI during follow-up; secondary endpoints included treatment and recovery from AKI. AKI was defined based on Kidney Disease Improving Global Outcomes criteria as an increase of serum creatinine levels > 1.5 times their baseline value after starting therapy. Cumulative incidences and Cox proportional hazard regression models were used to evaluate time to event data. Results: A total of 64 patients met inclusion criteria for the study (30 received CAR-T and 34 received teclistamab therapy). There were 14 AKI events occurring during follow-up (10 teclistamab [n = 6 stage 1, n = 3 stage 2 and n = 1 stage 3] and 4 CAR-T [n = 3 stage 1 and n = 1 stage 2]). Cumulative incidence estimates of AKI at 120 days after treatment were 32% (95% CI: 14%-47%) for teclistamab patients and 10% (95% CI: 0%-21%) for CAR-T patients. While patients receiving teclistamab were found to be at increased risk of an incident AKI event compared to patients receiving CAR-T therapy, results were not statistically significant (HR (95% CI): 3.38 (0.93-12.31), p = 0.065). Median time to development of AKI was 30 days (IQR 16, 73) in teclistamab and 59 days (IQR 9, 146) in CAR-T patients. Among the 10 patients in the teclistamab group with an AKI event, 4 (40%) had complete renal recovery and 4 (40%) had partial recovery, while among the 4 patients with CAR-T with an AKI event, 2 (50%) experienced complete renal recovery and 2 (50%) experienced partial recovery. Conclusions: Our study showed that almost one third of patients receiving teclistamab therapy for relapsed and refractory multiple myeloma experienced an incident AKI event during follow-up. This finding underscores the importance of monitoring for kidney function in these patients.

7516 Background: Immune effector cell hemophagocytic lymphohistiocytosis IEC-HS is a complication of CAR T cell therapy (CART). This study aims to look at the outcomes of CART patients who develop IEC-HS. Methods: Patients who developed IEC-HS after receiving CART and patients who developed IEC-HS without (nonCART) between December 2020 and March 2022 were included. Results: The 20 CART patients were older than the 25 nonCART patients. Peak ferritin, fibrinogen, CRP, serum creatinine and transaminases were similar between the 2 group. CART patients had lower white blood cell count and platelets and bilirubin than the nonCART patients. CART patients were more like to have markedly elevated IL-6 levels (> 315 mg/ml), higher IL-18, higher MCP-1, and suppressed IL-1β and GMCSF than nonCART patients (Table). Treatment of IEC-HS included tocilizumab (n = 19), anakinra (n = 18) siltuximab (n = 4) and basiliximab (n = 4), dexamethasone (n = 18) methylprednisolone (n = 6), etoposide (n = 1) and ruxolitinib (n = 1). A significant response defined by a 90% reduction or normalization of the cytokine was observed with IL-10 and IFN-ϒ in 92.3% and 84.6% of the CART patients respectively. An intermediate response was noted with TNF, IL-6, MCP-1 and MIP-1 in 38.4%, 30.8% and 61.6% and 38.5% of the patients respectively. No patient had a significant response in IL-2Rα or IL-1β and only 7.7% had a significant response in IL-18. Of the 5 patients who had a MIP-1 response, 4 were on basiliximab +/- high flow continuous venovenous hemofiltration and the only patient that had an IL-18 response was on both modalities. The 100-day mortality after IEC-HS in the CART patients was 40% and was associated with higher peak and lower best ferritin but not the percentage reduction (Table). Higher TNF (90.3 pg/ml vs 37.2 pg/ml, p = 0.05), markedly elevated levels of IL-6 (92% vs 50%, p = 0.03) and IL-10 (33% vs 0%) and an IL-6 response (44.4% vs 0%) were associated with survival at day 100. IL-6 responders had lower peak ferritin vs IL-6 nonresponders (14066 mcg/L vs 45051 mcg/L, p = 0.08). Enterococcus faecium bacteremia developed in 75% of the nonsurvivors vs 16.6% of the 100-day survivors (p = 0.009). Survivors cleared the enterococcus bacteremia within days while nonsurvivors had protracted bacteremia. Conclusions: IEC-HS is devastating complication of CART. Anti-cytokine therapy can reduce some cytokines and ferritin but overimmunosuppression may lead infectious complication, in particular with E. faecium. Better biomarkers are needed to finetune immunosuppressive therapy in order to avoid over-immunosuppression. [Table: see text]

Accurate assessment of GFR is crucial to guiding drug eligibility, dosing of systemic therapy, and minimizing the risks of both undertreatment and toxicity in patients with cancer. Up to 32% of patients with cancer have baseline CKD, and both malignancy and treatment may cause kidney injury and subsequent CKD. To date, there has been lack of guidance to standardize approaches to GFR estimation in the cancer population. In this two-part statement from the American Society of Onco-Nephrology, we present key messages for estimation of GFR in patients with cancer, including the choice of GFR estimating equation, use of race and body surface area adjustment, and anticancer drug dose-adjustment in the setting of CKD. These key messages are based on a systematic review of studies assessing GFR estimating equations using serum creatinine and cystatin C in patients with cancer, against a measured GFR comparator. The preponderance of current data involving validated GFR estimating equations involves the CKD Epidemiology Collaboration (CKD-EPI) equations, with 2508 patients in whom CKD-EPI using serum creatinine and cystatin C was assessed (eight studies) and 15,349 in whom CKD-EPI with serum creatinine was assessed (22 studies). The former may have improved performance metrics and be less susceptible to shortfalls of eGFR using serum creatinine alone. Since included studies were moderate quality or lower, the American Society of Onco-Nephrology Position Committee rated the certainty of evidence as low. Additional studies are needed to assess the accuracy of other validated eGFR equations in patients with cancer. Given the importance of accurate and timely eGFR assessment, we advocate for the use of validated GFR estimating equations incorporating both serum creatinine and cystatin C in patients with cancer. Measurement of GFR via exogenous filtration markers should be considered in patients with cancer for whom eGFR results in borderline eligibility for therapies or clinical trials.

e24143 Background: Accurate assessment of glomerular filtration rate (GFR) is crucial to guiding drug eligibility, dose-adjusting systemic therapy, and minimizing the risks of both undertreatment and toxicity in patients with cancer. To date, there has been a lack of guidance to standardize approaches to GFR estimation in the cancer population based on the available evidence. We aim to present data on the first systematic review (SR) of GFR estimating equations in patients with cancer. Methods: We conducted a SR on behalf of the American Society of Onco-Nephrology (ASON) on the accuracy of equations to estimate GFR in adult patients with cancer, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We required that studies use a reference methodology as comparator involving measured GFR via urinary or plasma clearance of an exogenous filtration marker or carboplatin. Two search strategies focusing on studies using serum creatinine (Cr) and cystatin C (Cys) were developed. Risk of bias and quality assessment was performed for all studies. Results: A total of 39 studies (21,949 patients in total, 19,025 with solid cancers) were included. Studies assessing populations in Europe were most frequent (50%), followed by Asia (27%) and the remaining from Australia/New Zealand and North and South America. Risk of bias and quality assessment allocated 15 studies (38%) as low or very low quality, and 24 (62%) as low-moderate or moderate quality. The most commonly assessed GFR estimating equations included Cockroft-Gault (32 studies), Modification of Diet Renal Disease (MDRD) (24 studies), Chronic Kidney Disese Epidemiology Collaboration Study (CKD-EPI)Cr (22 studies), Wright (13 studies), CKD-EPICys (8 studies), CKD-EPICr-Cys (8 studies), and Jeliffe (8 studies). Given the importance of accurate and timely eGFR assessment and the evidence supporting the performance (i.e., accuracy) of the CKD-EPI incorporating both Cr and Cys, we suggest the use of this equation in patients with cancer (grade 2C). Where Cys is unavailable, CKD-EPICr is the next preferred equation given the supporting data for its performance and widespread availability. Since included studies were moderate quality or lower, the ASON rated the certainty of evidence as low. Also, additional data on clinical outcomes related to the selection of eGFR equations is needed. We suggest measurement of GFR via an exogenous filtration marker in patients with cancer for whom eGFR results in borderline eligibility for therapies or clinical trials (ungraded). Conclusions: Based on the results of this SR, we suggest use of contemporary methods for estimation of GFR (CKD-EPICr-Cys and CKD-EPICr-Cr) and avoidance of older and less accurate formulae such as Cockcroft-Gault.

Introduction: Monoclonal gammopathy of renal significance (MGRS) is characterized by clonal cell deposition of monoclonal immunoglobulin causing renal manifestations without overt malignancy. MIDD is a subtype of MGRS characterized by deposition of monoclonal light (LCDD), heavy chains (HCDD), or both (LHCDD) along the renal glomerular and tubular basement membranes. Virtually all organs can be involved, and if left untreated, MIDD can progress to MM and end stage renal disease. Although these patients classically did not receive treatment, current MIDD management is primarily focused on controlling the underlying clonal plasma cell disorder. Case description: We present a 56-year-old male with atypical MIDD treated successfully with plasma cell directed therapy consisting of daratumumab, cyclophosphamide, bortezomib, and dexamethasone (DARA-CYBOR-D). Despite a primary diagnosis of diabetic kidney disease, renal biopsy suggested myeloma-related MIDD based on linear immunofluorescent staining for IgG and kappa light chains along the tubular and glomerular basement membranes. Notably there were no electron dense deposits in the mesangium or tubular basement membranes typical to MIDD electron microscopy. Despite the presentation of MIDD on IF only, DARA-CYBOR-D treatment led to hematologic and renal improvement and remission from MIDD, with a GFR increase from 22 to 59 mL/min/BSA and a drop in urine protein from up to 9 to 0.6 g/dL. Conclusions: In conclusion, our case illustrates the efficacy of the DARA-CYBOR-D regimen in a patient with IF-only MIDD. We highlight the importance of obtaining a kidney biopsy when there are other potential causes for real decline and enhance our understanding of pathological and clinical spectrum of MIDD.

Abstract Background and Aims Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) has a poor renal prognosis and a high rate of recurrence after kidney transplantation, up to 90%, typically within the first-year post-transplant. Nearly 50% of patients lose their renal allograft within 3 years of recurrence. It has been suggested that pretreatment therapy (with B cell depleting or plasma-cell directed therapy) can help prevent recurrence or modulate the course of disease post-transplant. The aim of our study is to evaluate the effect of pretreatment therapy given within 6 months prior to kidney transplant on outcomes including PGNMID recurrence and all cause graft loss. Method Between 1996 and 2022, a total of 28 patients with biopsy-proven PGNMID as the cause of end stage kidney disease received a total of 31 kidney transplants. All patients had at least one year of follow-up data, for all but one patient this included surveillance kidney transplant biopsies completed at our center. Recurrence was defined histologically by immunofluorescence finding of monoclonal immunoglobulin deposits, independent of other histological or clinical parameters. The incidence of recurrence and all cause graft loss were analyzed by Kaplan-Meier plots. Results Median age of patients at transplant was 57 years, 87% were white, 65% were male, 74% received living donor transplant, 59% received thymoglobulin induction, 81% received maintenance with tacrolimus, mycophenolate, and prednisone. Median follow up time was 80 months. A total of 9 patients received pretreatment within 6 months of transplant, 8 received Rituximab and one received Daratumumab. The pretreatment group was generally younger at transplant (53 years vs 57 years) and had a shorter median follow up time (65 months vs 96.5 months), but neither were statistically significant. Overall recurrence rate was 78% for pretreatment and 91% for control, though difference in time to recurrence was not statistically significant (Fig. 1). The difference in all cause graft loss between groups was not statistically significant, however, none in the pretreatment group had graft loss by 60 months (Fig. 2). One patient who received daratumumab had no recurrence by 1 year post-transplant. Conclusion In kidney transplant recipients with PGNMID, pretreatment (primarily with rituximab) may be modulating the post-transplant course of disease. Further studies are needed to determine the extent of this effect and if plasma-cell directed vs B-cell directed therapy may be superior.