Myeloma Kidney Research Articles

The Role of Monoclonal Antibodies in the Treatment of Myeloma Kidney Disease.

Renal failure is one of the most important manifestations of multiple myeloma. It is caused by renal lesions such as cast nephropathy, immunoglobulin deposition disease, AL amyloidosis or other glomerular and/or tubular diseases, mostly due to the toxic effect of free light chains in serum. Renal failure can represent a clinical emergency and is associated with poor outcome in newly diagnosed and relapsed/refractory multiple myeloma patients. Although progression-free survival and overall survival have improved with the introduction of novel agents, renal failure remains a challenge for the treatment of patients with multiple myeloma. Monoclonal antibodies are a component of therapy for newly diagnosed and relapsed/refractory patients and, based on clinical trials and real-world experience, are also safe and effective for subjects with renal failure, even if they are on dialysis. Most of the data are on anti-CD38 and anti-SLAM7 antibodies, but new antibody-drug conjugates such as belantamab mafodotin and bispecific antibodies also appear to be effective in myeloma kidney disease. In the future, we will have to face some challenges, such as defining new criteria for renal response to treatment, defining specific trials for these difficult-to-treat patients and integrating different therapeutic options.

Pomalidomide Use and Kidney Outcomes in Patients With Relapsed/Refractory Multiple Myeloma and Chronic Kidney Disease: A Real-World, Population-Based Cohort Study

BackgroundPomalidomide-based regimens are the cornerstone of treatment for relapsed/refractory MM (RRMM). Despite the high incidence of chronic kidney disease (CKD) in RRMM, individuals with advanced CKD have been excluded from phase II/III RCTs, creating a gap in our understanding of the effects of pomalidomide use in patients with RRMM complicated with advanced CKD. We undertook a cohort to study to understand the efficacy safety of pomalidomide-based regimens among patients with CKD using real-world data. MethodsPopulation-based, cohort study of patients ≥ 18 years with RRMM treated with pomalidomide in Ontario, Canada. Primary outcome was all-cause mortality. Secondary outcomes were time-to-major adverse kidney events (MAKE), time-to-next treatment, kidney response and safety. ResultsTotal 748 patients with RRMM utilizing pomalidomide were included; 440 had preserved kidney function, 210 had moderate CKD (eGFR 30-59 mL/min/1.73m2), and 98 had advanced CKD (eGFR < 30 mL/min/1.73m2). Mean age was 70.2 years, 43.3% were women. Patients with advanced CKD had a higher risk of all-cause mortality compared to the preserved kidney function group (aHR 1.37, 95% CI 1.06, 1.78). MAKE was higher in advanced CKD (aHR 1.70, 95% CI 1.03, 2.35). Kidney response was similar between moderate and severe CKD groups (aOR 1.04, 95%, CI 0.56-1.90). Safety outcomes were similar between groups. ConclusionsPatients with advanced CKD and RRMM on pomalidomide-based regimens exhibited reduced survival and a higher risk for MAKE. However, the probability of experiencing some degree of kidney recovery is 50% in both moderate and severe CKD, with comparable safety outcomes.

635 - Impact of race on renal recovery in patients with new diagnosis of multiple myeloma and acute kidney injury requiring dialysis

635 - Impact of race on renal recovery in patients with new diagnosis of multiple myeloma and acute kidney injury requiring dialysis

Acute myeloma kidney and SARS-COV2 infection with dialysis need: never say never - a case report

BackgroundOlder individuals with multiple comorbidities and especially patients with multiple myeloma are at higher risk of contracting SARS-CoV-2. When patients with multiple myeloma (MM) are also affected by SARS-CoV-2 the time to start immunosuppressants is still a clinical dilemma especially when urgent hemodialysis is required for acute kidney injury (AKI).Case presentationWe present a case of an 80-year-old woman who was diagnosed with AKI in MM. The patient began hemodiafiltration (HDF) with free light chain removal combined with bortezomib and dexamethasone. The reduction of free light chains concurrently was obtained by means of HDF using poly ester polymer alloy (PEPA) high-flux filter: 2 PEPA filters were used in series during each 4-h length HDF session. A total of 11 sessions was carried out. The hospitalization was complicated with acute respiratory failure caused by SARS-CoV-2 pneumonia successfully treated with both pharmacotherapy and respiratory support. Once the respiratory status stabilized MM treatment was resumed.The patient was discharged in stable condition after 3 months of hospitalization. The follow up showed significant improvement of the residual renal function which allowed interruption of hemodialysis (HD).ConclusionsThe complexity of patients affected by MM, AKI, and SARS-CoV-2 should not discourage the attending physicians to offer the adequate treatment. The cooperation of different specialists can lead to a positive outcome in those complicated cases.

#5831 LIGHT CHAIN REMOVAL IN MULTIPLE MYELOMA PATIENTS WITH HFR-SUPRA HEMODIALYSIS: OUR EXPERIENCE

Abstract Background and Aims Kidney injury is a common complication in multiple myeloma (MM) and it has a negative prognostic implication. Most common cause of Acute Kidney Injury (AKI) in these patients is Light chain Cast Nephropathy, where free light chains precipitate in the tubules and bind with uromodulin, turning into intratubular casts that obstruct the tubules and also promote local giant cell reaction and interstitial inflammation and fibrosis. Free light chains (FLCs) can also damage the kidneys due to direct tubular toxicity when excessive amounts are reabsorbed by the proximal tubules. Targeted therapy to reduce FLC load can help recover renal function. Both total reduction and reduction speed are relevant for prognosis. FLC removal through extracorporeal techniques can be used as an adjuvant therapy, having an important part on the evolution of the disease. We gathered data from our experience treating MM patients with AKI with HFR-supra hemodialysis (HD) and analized the evolution and possible influence of this technique on renal recovery. Method This is an observational retrospective study. We included all patients with a diagnosis of multiple myeloma and acute kidney injury who received HFR-Supra hemodialysis in between years 2016-2022 in Hospital Virgen Macarena (Seville). We initially performed 6-10 daily HFR-Supra HD sessions and then modulated the frequency based on renal response (if renal replacement therapy had to be continued they underwent a usual hemodialysis regime 3 days a week). We continued these sessions until renal recovery was achieved or free light chain levels were reduced in agreement with the Hematology team. Measurement of pre and post dialysis FLCs was made always at first and last session and at least once in between, depending on the total number of sessions. Results 12 patients, with mean age at diagnosis 63.6 (43-86) years, presented with AKI stage KDIGO 3. 1 of them was oliguric. Median serum creatinine at diagnosis was 4.4 mg/dL [2,2-17], mean proteinuria was 4,1g/24 h [0,7-8,7] and 66,7% had positive Bence Jones proteinuria (mean 2,3g/24 h). 2 of the patients had previous chronic kidney disease stage 3a. All of them were diagnosed with Light Chain Multiple Myeloma (75% kappa, mean 10346 mg/L; 25% lambda, mean 5990 mg/L). Mean clonal bone marrow plasma cell was 20,7% [2-55]. According to the Revised International Staging System (R-ISS), 25% were stage 2 and 75% were stage 3. Renal biopsy was performed in 4 patients, all showed evidence of Cast Nephropathy. The indication for starting HFR-Supra HD was FLC removal in 9 patients, need of renal replacement therapy in 1 and both in 2 patients. We have experience in our center with using this therapy as an adyuvant treatment and often we start the technique in patients who present with AKI but would not necessarily have immediate need for renal replacement therapy. The goal is to remove FLCs and avoid further damage to the kidney tissue. Out of the 12 patients, 9 were able so stop dialysis (75%). They received a mean number of 12,4 [3-41] sessions in 3,7 [0,2-25] months). Free light chain removal per session was 24% on average [5-43%]. All of them were started on bortezomib-dexamethasone regime as initial chemotherapy for MM. As per renal recovery, at 3 months 33,3% achieved complete response, 11,1% partial response and 55,6% minimal response. At 1 year, 42,9% achieved complete response, 14,3% partial response and 42,9% minimal response. One-year survival rate was 91,7% (1 patient died from respiratory sepsis less than 1 month after diagnosis). Conclusion HFR-Supra hemodialyisis achieved a 24% free light chain removal per session on average. After presenting severe AKI (KDIGO 3), almost 43% of patients who received this adyuvant therapy obtained full renal recovery at 1 year and in 75% of patients withdrawal from hemodialysis was possible. 1 year survival was 91,7%.

Multiple Facets of Multiple Myeloma in Kidney Biopsy: A Multicenter Retrospective Study.

Multiple myeloma is a type of plasma cell dyscrasia, which causes clonal proliferation of plasma cells and deposition in various organ systems. At presentation, 50% of patients with multiple myeloma have kidney dysfunction, which is considered a poor prognostic indicator. Data on the histopathological manifestations of multiple myeloma are sparse. To look at the kidney histopathological lesions in patients with the clinical diagnosis of multiple myeloma. A retrospective analysis of all kidney biopsies in patients with the clinical diagnosis of multiple myeloma was performed from June 1, 2020 to May 30, 2022, from three tertiary care nephrology referral centers. A total of 61 patients with multiple myeloma and biopsy-proven kidney involvement were included in the study. The mean age at presentation was 55.39 ± 11.91 years, with male predominance (male to female ratio -1.6:1). The most common lesion on kidney biopsy was myeloma cast nephropathy (72.1%), followed by light chain deposition disease (21.3%) and AL amyloidosis (18%). About 26% of patients had dual lesions on kidney biopsy, 3% had three types of lesions on kidney biopsy In 48% of patients, the diagnosis of multiple myeloma was made only after the kidney biopsy. Patients with multiple myeloma and kidney involvement should be biopsied as the type of histopathological lesion influences the treatment options and prognosis.

A case of multiple myeloma with unusual presentation

Extramedullary plasmacytoma is a rare and unusual complication of multiple myeloma (MM). Some sites for the extramedullary involvement of MM are the liver, spleen, lymph node, lung, and skin. Renal failure is another complication of MM due to myeloma kidney, uric acid nephropathy, hemoconcentration, or light chain disease. This study reported a case of MM with unusual presentation. She was a 61-year-old woman who was admitted to the internal ward due to severe renal failure, anemia, mild proteinuria, hypertension, thrombocytopenia, and soft tissue mass in both lungs in the spiral computed tomography (CT) scan. In the skull X-ray, there was not any lytic lesion. Further, plasma cells greater than 30% were observed in serum protein electrophoresis pick of gamma region and in the bone marrow aspiration, so the final diagnosis of the patients was MM with extramedullary plasmacytoma.

Multiple Myeloma and Acute Kidney Injury: Mechanisms Involved

The renal manifestations of multiple myeloma are devastating coupled with a disease as aggressive as the aforementioned. Its pathophysiological understanding has been clarified over time and has revealed the different mechanisms by which difficult-to-manage kidney damage occurs. However, the different therapies that have been developed have made this disease have an increasingly better prognosis. It is still a therapeutic challenge to treat myeloma together with a disease as complex as kidney disease.

Multiple Myeloma and Acute Kidney Injury: Mechanisms Involved

Multiple Myeloma and Acute Kidney Injury: Mechanisms Involved

Early Light Chains Removal and Albumin Levels with a Double Filter-Based Extracorporeal Treatment for Acute Myeloma Kidney.

Renal impairment in Multiple Myeloma (MM) represents one of the most important factors that influences patient survival. In fact, before the introduction of modern chemotherapy, less than 25% of patients with acute kidney injury (AKI) and MM who required dialysis recovered sufficient renal function to become independent from dialysis, with a median overall survival of less than 1 year. There are many other factors involved in determining patient survival. In this study we aimed to investigate the role of double filter-based extracorporeal treatment for removal of serum free light chains (sFLC) in acute myeloma kidney (AKI for MM) and to evaluate patient overall survival. All patients received Bortezomib-based chemotherapy and extracorporeal treatment for sFLC removal. For each session 2 dialyzers of the same kind were used. The dialytic dose was not related to the degree of renal function but to the removal of sFLC. The factors that have been found to be significantly associated with lower mortality were reduction of sFLC at day 12 and day 30, >50% reduction of sFLC at day 30, number of sessions and independence from dialysis. Among baseline characteristics, albumin level was statistically associated with the patients’ outcome. Our analysis highlights the importance of the early treatment for removal of sFLC in AKI for MM. These results indicate that the early removal of sFLC can improve patient’s outcome.

MO173: Clinical Profile of Plasma Cell Dyscrasias and Their Renal Outcomes

Abstract BACKGROUND AND AIMS The involvement of kidney in plasma cell dyscrasias is widespread, often referred to as myeloma kidney. At the time of presentation, nearly 50% of patients have renal involvement which is associated with higher mortality [1, 2]. Multiple myeloma is more common in African Americans, with male predilection and median age about 65–70 years [3]. Two major causes of renal insufficiency are light chain cast nephropathy and hyperkalcaemia [4]. Flow cytometry plays an important role in diagnosis of plasma cell dyscrasias. Myeloma cells infrequently express CD19 and variable CD45 in contrast to normal plasma cells. Approximately 70% of myeloma cells will express CD56, which is typically negative in normal plasma cells and in plasma cell leukaemia [5]. Studies addressing the relation of flow cytometry parameters with respect to prognosis and outcome in plasma cell dyscrasias are sparse in Asian population. Hence, this research was conducted to study the clinical profile and correlation of flow cytometry parameters with renal outcomes in patients with plasma cell dyscrasias. METHOD All consecutive patients, aged above 18 years and diagnosed with plasma cell dyscrasias from January 2016 to June 2021 were included. RESULTS Of 165 patients, 115 were males (69.7%), with mean age 58.2 ± 6.4 years. Pallor was seen in 126 (76.4%), bone pains in 90 (54.5%), lytic lesions in 63 (38.2%) and fractures in 37 (22.4%) patients. Severe anaemia (&amp;lt;7 g/ dL) was seen in 35 (21.2%) patients. At presentation, deranged renal parameters with eGFR &amp;lt; 60 mL/min/1.73 m2 were seen in 89 (53.9%) patients, of which 55 (61.8%) patients progressed to chronic kidney disease and 8 (8.9%) patients were continued on maintenance hemodialysis. Nephrotic syndrome presentation was seen in 26 (15.8%) patients. Infections were seen in 65 (39.4%) patients, of which most common infections were respiratory (25, 38.5%), blood stream (18, 27.7%) and urinary tract (12, 18.5%) infections. Serum free light chains were more than 800 mg/L in 71 patients, of them high kappa and lambda levels are seen in 41 (24.8%), and 30 (18.2%) patients, respectively. Most common immunoglobulin seen was IgG (63.6%), followed by IgA (15.8%) and IgE (2.4%). Flow cytometry parameters are shown in Table 1. Remission was attained with chemotherapy in 139 patients (64.3%), and bone marrow transplantation was done in 27 patients (16.4%). Relapse of disease was seen in 31 patients (18.8%) and worsening of renal parameters at relapse was seen in 15 (48.4%) patients. A total of 35 (21.2%) patients expired. Correlation of flow cytometry parameters with renal outcomes showed presence of CD56 with worse renal outcomes (P = .032), and presence of CD117 with favourable renal outcomes (P = .003) with statistical significance. Presence of CD56 and CD138 had increased risk of mortality with significant P value (P = .04, P = .01, respectively). CONCLUSION Flow cytometry parameters may play a role in predicting the prognosis and renal outcomes in patients of plasma cell dyscrasias. Our study showed presence of CD56 with worse renal outcome and mortality, while CD117 presence with favourable renal outcome. Table 1. Flow cytometry parameters in patients with plasma cell dyscrasias CD markers (n = 165) Present Absent CD19 21/165 (12.7%) 144/165 (87.3%) CD38 53/165 (32.1%) 112/165 (67.9%) CD45 46/165 (27.9%) 119/165 (73.9%) CD56 134/165 (81.2%) 31/165 (18.8%) CD117 86/165 (52.1%) 79/165 (48.9%) CD138 46/165 (27.9%) 119/165 (73.9%) KAPPA 93/165 (56.4%) 72/165 (44.6%) LAMBDA 71/165 (43%) 94/165 (57%)

Light Chain Cast Nephropathy in Multiple Myeloma: Prevalence, Impact and Management Challenges.

“Cast nephropathy” (CN) is a pathological feature of myeloma kidney, also seen to a lesser extent in the context of severe nephrotic syndrome from non-haematological diseases. The name relates to obstruction of distal tubules by “casts” of luminal proteins concentrated by intensive water reabsorption resulting from dehydration or high-dose diuretics. Filtered proteins form complexes with endogenous tubular Tamm-Horsfall glycoprotein. The resulting gel further slows or stops luminal flow upon complete obstruction of distal convoluted tubules and collecting ducts. Thus, a tubular obstructive form of acute kidney injury (AKI) is a common consequence of CN. The pathogenesis of CN will be reviewed in light of recent advances in the understanding of monoclonal disorders of B lymphocytes, leading to the release of immunoglobulin components (free light chains, FLC) into the bloodstream and their filtration across the glomerular basement membrane. Treatment aiming at reduction of the circulating burden of FLC may help recovery of renal function in a fraction of these patients, besides filling the void between the onset of AKI, histopathological diagnosis, and full response to pharmacologic treatment.

Renal recovery after acute kidney injury requiring urgent hemodialysis is not associated with improved survival of the patients with multiple myeloma.

Severe acute kidney injury (AKI) requiring urgent hemodialysis (uHD) is associated with considerable morbidity and mortality in patients with multiple myeloma (MM). To evaluate the renal function, outcome, and survival status of patients with MM who received uHD and to compare their overall survival with MM patients who did not receive uHD. A total of 70 eligible MM patients who received uHD were included together with 70 control patients with MM. In the study group, 11 patients (15.7%) were known to have pre-existing chronic kidney disease. Thirty-four percent of the study group had AKI requiring uHD at MM diagnosis. Seventy-eight percent of the study group had severe AKI due to myeloma kidney. Renal function recovered in 36 patients (51.4%). Patients with MM who became hemodialysis dependent had significantly higher serum creatinine (sCr) levels at the time of AKI compared to patients with renal recovery (p < 0.05). Logistic regression analysis showed that high sCr on admission was significantly associated with hemodialysis dependence (odds ratio 0.78; 95% CI: 0.63-0.96; p = 0.018). The median overall survival was 30months [IQR: 26] in the study group and 84months [IQR: 96.25] in the control group (p < 0.05). Cox regression analysis showed that the need for uHD at initial MM diagnosis was associated with reduced survival (hazard ratio (HR) 1.9; 95% CI: 1.1-3.2; p = 0.017). Renal recovery did not provide a survival benefit. The need for uHD was associated with poor survival. Recovery of renal function was not associated with improved survival.

Management of a newly diagnosed case of myeloma kidney in a recently COVID-19 recovered patient

Management of a newly diagnosed case of myeloma kidney in a recently COVID-19 recovered patient

Compromiso renal en gammapatías monoclonales

IntroductionThe kidney is one of the organs most frequently affected by disease processes which produce monoclonal immunoglobins, therefore renal morphological and immunopathological alterations should be clearly recognized. ObjectiveTo describe the pathological features of renal involvement in monoclonal gammopathies. Material and methodsA descriptive, retrospective and cross-sectional study of renal biopsies studied in a single center during a period of 14 years was carried out. Results102 cases were included, of which 53% were male patients and the median age was 62.5 years (range 34 - 79). 97% of the biopsies were from native kidneys. The most frequent histopathological diagnosis (31.4%) was myeloma kidney, with kappa being the light chain most frequently deposited (65.6% of cases). AL amyloidosis was the second most common (29.4%) where the lambda chain predominated in 86.6%, followed by light chain deposition disease (20.6%) with the predominance of the kappa chain in 66.6%. ConclusionsThe most frequent renal involvement due to monoclonal gammopathies was myeloma kidney with deposition of kappa light chains, followed by AL lambda amyloidosis; these diseases were found more frequently in patients over 50 years of age.

Rapid Removal of Myeloma Light Chains By Continuous Veno-Venous Hemofiltration in a Patient with Acute Cast Nephropathy As a Result of Lambda Light Chain Myeloma

Myeloma cast nephropathy or myeloma kidney (MK) is a complication observed in up to one third of patients with multiple myeloma (MM). MM patients who recover kidney function have longer remissions and increased overall survival. Previous attempts at light chain reduction with the use of plasma exchange in addition to chemotherapy have not consistently improved patient outcomes and remains an area of research. The inefficiency of plasma exchange is due to the high volume of distribution of light chains in the extravascular space which will repopulate the vascular space once the exchange procedure is complete.Continuous Veno-Venous Hemofiltration (CVVH) is a form of continuous hemodialysis (HD). The use of CVVH in addition to chemotherapy in MK is rational, as continuous filtration allows for ongoing equilibrium between the extravascular and intravascular compartments, thus reducing the total body MM protein load. The Purema 500 (NxStage Medical, Lawrence, MA) filter used for CVVH has an average pore size of 65 kDa, and albumin Sieving co-efficient of 0.05. The myeloma kappa light chain is approximately 25 kDa whereas the lambda light chain (LLC), circulating as a dimer, is approximately 45 kDa and the average IgG complex is approximately 150 kDa. These data suggest that CVVH filtration could reduce the light chain MM protein in patients with MK, but would likely be ineffective for IgG, IgA or IgM MM.This hypothesis was tested in a 60 year-old-man with known normal baseline kidney function and LLC MM, who developed MK in the perioperative period, of a hip stabilization procedure, at the time of MM recurrence. Biopsy showed the kidney failure was due to MK. The LLC concentration at the time of kidney failure was 3,750 mg/L. We employed CVVH, run 24 hours a day for 72 hours, with concurrent high dose intravenous dexamethasone 40mg days 1-4 and IV bortezomib 1.3mg/m2 days 1,4,8, 11.Serum protein electrophoresis (SPEP) obtained prior to CVVH showed a monoclonal spike of 6.7 g/L or 11.5% of the total protein (figure 1A). Protein electrophoresis (PEP) of the first bag of spent dialysate showed a restricted peak 1.1g/L or 2.1% of the total protein with a similar appearance to the monoclonal spike on the SPEP, demonstrating removal of the LLC by CVVH (figure 1B). 72 hours after the initiation of CVVH and chemotherapy, the LLC concentration decreased 77% from 3,750 to 850 mg/L (figure 1D), SPEP showed the monoclonal spike had decreased to 0.5 g/L or 1% of the total protein (figure 1C). The patient became dialysis independent three months following CVVH.Previous series have reported on 11 patients with acute MK, who have been treated with as specialized high cut-off hemodialysis (HCO-HD) filter, which has a pore size of 45 kDa, and concurrent chemotherapy. Seven of these patients (63%) became dialysis independent. These studies showed an overall reduction of serum light chain protein in their patients, but did not report if the light chains were present in the dialysate. The EUropean trial of free LIght chain removal by exTEnded haemodialysis in cast nephropathy (EuLITE) reported an improved rate of renal recovery 33% vs 43% with the use of HCO-HD versus standard HD.By way of comparison, CVVH, which is widely available in the United States, rapidly decreased the LLC myeloma protein. Our data supports the depletion of the LLC stores in the extravascular compartment as we did not see a rebound of LLC after stopping CVVH (figure 1D). As kappa light chains have a lower molecular weight than LLC, we would expect the same result with kappa light chain MM. Patients with IgG MK may also benefit from CVVH, as we saw proteins with a molecular weight higher than 65 kDa in the spent dialysate PEP, including proteins in the IgG range (figure 1C). CVVH filters lead to less protein wasting as compared to the HCO-HD filters which would negate the need for albumin replacement. The observed rapid rate of decline of the light chain concentration in this case supports the addition of CVVH to chemotherapy, as the clearance of the myeloma protein was more rapid than has been described in previous trials using bortezomib and dexamethasone alone. Randomized clinical trials would need to be conducted to know if this approach is superior to chemotherapy alone. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Plasmapheresis and Myeloma Cast Nephropathy: A Meta-Analysis and Review of Evidence

Introduction:Cast nephropathy is the most form of kidney disease in patients with multiple myeloma and it can be associated with worse prognosis. To this date, the role of plasmapheresis in this patient population remains unclear with conflicting evidence. We performed this meta-analysis and reviewed the available evidence for the effect of plasmapheresis in myeloma patients with cast nephropathyMethods:Protocol registered at PROSPERO 2016 (CRD42016033377). We searched PubMed, Embase, Medline, and Cochrane library for all eligible randomized controlled trials which looked into the role of plasmapheresis in cast nephropathy patients from 1980 to 2017. Eligible studies were reviewed separately by 2 authors and any conflict was resolved by referring to a third author. Our search strategy resulted in a total of 511 articles. We screened the titles and abstracts for relevance. English only randomized controlled trials which looked into the effect of plasmapheresis on renal outcome in cast nephropathy patients were considered. A full text was obtained in case of uncertainty about the content. We used the Cochrane's tool for risk of bias and quality assessment. Studies were reviewed and data was extracted independently by two authors, and final judgment was made after collaboration between authors. A confirmed diagnosis of multiple myeloma with myeloma kidney disease as evidenced by either presence of high light chain concentration in the urine or by kidney biopsy was required to include patients in our analysis. Six controlled trials were initially identified of which 3 were excluded since they were early reports of a larger trial. Three trials were included in our final analysis based on the inclusion criteria. Our primary outcome was to assess the risk of dialysis dependence at 6 months cast nephropathy patients when treated with plasmapheresis along with chemotherapy compared to those who do not receive plasmapheresis. Secondary outcome was to assess mortality at 6 months for both groups. Data analysis was performed using Review Manager version 5.3.5. The measurement of effect was done by calculating the risk ratio and 95% confidence interval using a fixed-effect Mantel-Haentszel method. We assessed for heterogeneity using Mantel-Haentszel chi-square test and I2 test.Results:A total of 147 patients were analyzed in this study (84 patients in the plasmapheresis group and 63 patients in the chemotherapy group). Plasmapheresis treatment schedule varied between the studies, and ranged between 4 and 7 sessions. Table 1 summarizes the included studies, and table 2 shows serum creatinine level, presence of cast nephropathy at presentation, and urine protein level at presentation and after treatment for each group.There was a significantly lower risk of dialysis dependence in the plasmapheresis group compared to the control group (Risk Ratio = 0.45; 95% CI, 0.23-0.86, P = 0.02), (Figure 1). No statistically significant difference in mortality risk at 6 months was found between the 2 groups; 22 patients died in the plasmapheresis group compared to 19 patients in the control group (Risk Ratio = 0.83; 95% CI, 0.49-1.40, P = 0.49).Discussion:Early reduction of free light chains has been shown to be associated with improved renal recovery. Using plasmapheresis along with chemotherapy to achieve this early reduction is one of the methods that has been evaluated in several studies, with variable results. The Myeloma and Renal Impairment Trial investigating the use of dexamethasone and chemotherapy with or without plasmapheresis in patients with newly diagnosed multiple myeloma and acute kidney failure, was supposed to be the largest randomized controlled trial to date. Unfortunately it closed prematurely due to slow recruitment. It is important to note that all trials were done before the introduction of proteasome inhibitors and immunomodulators, which has changed the course of multiple myeloma, and significantly improved complete remission, time to progression, progression free survival, and overall survival compared to conventional chemotherapy. Despite the conflicting evidence of plasmapheresis benefit in cast nephropathy patients, it still might be beneficial in some cases with biopsy proven cast nephropathy when possible and only after prompt initiation of chemotherapy. High-cutoff dialysis might be another promising alternative and clinical trials assessing this method are under the way. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Carfilzomib Is Safe and Effective in Newly Diagnosed Patients with Multiple Myeloma with Renal Involvement

Background. Carfilzomib is a proteasome inhibitor, currently approved for use in relapse-refractory Multiple Myeloma (RRMM).1 There is mixed data on safety of Carfilzomib in patients (pts) with renal impairment (RI) and minimal in the upfront setting, partly due to exclusion of these pts from trials. Pooled data from phase 2 studies of single-agent Carfilzomib in RRMM, noted 24.1% acute kidney injury (AKI), including 23.8% of pts with moderate to severe renal dysfunction (CrCl<50 mL/min).2 Interestingly, severity of renal insufficiency did not have an effect on incidence of toxicity nor overall response rate.3 However, in FOCUS (single agent Carfilzomib vs Dexamethasone +/- Cyclophosphamide in RRMM), grouped renal events were three times more common in patients with baseline CrCl<30ml/min than those with CrCl>50 ml/min.4We previously reported on 71 pts receiving induction Carfilzomib, whose baseline RI was associated with incidence of AKI. Of pts with normal renal function, 36% developed AKI, compared to 59% and 62.5% of those with mild and moderate impairment, respectively.5 Current management dictates dose reduction only once CrCl ≥ 15ml/min.6 The aim of this retrospective study is to report on the safety profile and efficacy of induction Carfilzomib in pts with RI of newly diagnosed MM as evidenced by proteinuria.Methods. Patients were selected from the CarBiRd study (induction Carfilzomib and Dexamethasone; with subsequent Clarithromycin, Lenalidomide, and Dexamethasone; with Lenalidomide maintenance) at the Weill Cornell Medicine Myeloma Center. Pts were grouped based on renal involvement of myeloma. Baseline renal function was established by measuring pre-enrollment GFR using the Modification of Diet in Renal Disease (MDRD) equation. Subjects were stratified into 3 sub-groups: normal function (GFR>80 ml/min/1.732), mild impairment (GFR 50-80 ml/min/1.732), and moderate impairment (GFR 30-49 ml/min/1.732). Incidence of AKI was assessed during induction with Carfilzomib and Dexamethasone only. AKI was defined by increased serum creatinine (sCr) according to the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4.0.6 sCr and m-protein were measured prior to therapy and upon completion of Carfilzomib/dex induction. Overall response and toxicity were also assessed.Results. 75 patients were enrolled in the CarBiRd study. One withdrew for fever and AKI. Of the 61 patients with evaluable urine m-protein, 23 had normal kidney function, 15 mild impairment, and 3 moderate impairment. AKI was seen in 34.8% of patients with normal renal function, 53.3% with mild and 33.3% with moderate impairment. Of the 17 patients who had AKI, 70.6% had a return sCr within 0.15 mg/dl of baseline. Mean number of cycles of Carfilzomib was 5 (range 3-12). The mean fall in m-protein at end Carfilzomib was 87.4%.Of patients without proteinuria, 10 had normal kidney function, 7 had mild impairment, and 3 had moderate impairment. In pts with normal function 40% developed AKI, whereas those with mild and moderate impairment reported 71.4% and 66.6%, respectively. Mean number of cycles of Carfilzomib was 6.2 (range 3-14). Of the 11 patients who developed AKI, 91% had a return to serum creatinine within 0.15 mg/dl of baseline.Discussion. Data on renal toxicity of carfilzomib in patients with renal involvement of myeloma are limited to date, confounded by exclusion of renal impairment from studies, data mainly in the RRMM setting where prior or concurrent drug exposure may play a role. Previous data indicate baseline renal impairment may predict AKI. We report on a cohort of pts with newly diagnosed myeloma who received carfilzomib/dexamethasone induction, where renal involvement did not predict increased toxicity. In addition, most cases of reported AKI resolved prior to next week dosing, and required no intervention beyond hydration. We acknowledge the small cohort and single-arm, single-center nature of the study. As seen previously, response to therapy does not appear to be affected by renal impairment. At this time, myeloma kidney and decreased GFR should not preclude use of carfilzomib in pts with myeloma. [Display omitted] DisclosuresPerry:celgene: Honoraria. Pekle:celgene: Honoraria; BMS: Honoraria. Niesvizky:BMS: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Amgen: Consultancy. Rossi:Thrassos: Consultancy; Celgene: Consultancy.

Crystalline appearance in light chain cast nephropathy is associated with higher early mortality in patients with newly diagnosed multiple myeloma

BackgroundLight chain cast nephropathy (LCCN) is the most common kidney lesion in multiple myeloma patients. LCCN may exhibit a crystalline appearance. The frequency and clinical significance of crystalline LCCN are not well understood. Here, we report the first retrospective study of crystalline LCCN. MethodsTwenty-six patients with LCCN were enrolled. We studied the clinicopathological features and outcomes of LCCN patients and compared ordinary LCCN patients (n = 18) with crystalline LCCN patients (n = 8). ResultsCrystalline LCCN was not rare (8/26, 30.8%) in our study. The median age of LCCN patients was 57.5 (range, 41–75) years. No patients presented with nephrotic syndrome. No significant differences in clinical features were observed between the two groups. All crystalline LCCN patients suffered from advanced multiple myeloma and acute kidney injury. There was a dominance of the λ isotype (7/8, 87.5%) in patients with crystalline LCCN. Patients with ordinary LCCN had significantly higher scores of tubular atrophy and acute tubular injury than those with crystalline LCCN. The crystalline casts of 5 crystalline LCCN patients stained negative with antihuman Tamm-Horsfall glycoprotein. There were no significant differences in the median overall survival between the crystalline LCCN group and the ordinary LCCN group (6.0 months vs. 35.0 months, p = 0.173). However, crystalline LCCN patients had higher early mortality than ordinary LCCN patients (50.0% vs 11.1%, p = 0.03). ConclusionCrystalline LCCN patients had higher early mortality than ordinary LCCN patients. Thus, for patients with LCCN, crystalline appearance should be screened carefully.

MO182CRYSTALLINE LIGHT CHAIN CAST NEPHROPATHY IS ASSOCIATED WITH EARLY MORTALITY IN PATIENTS WITH MULTIPLE MYELOMA

Abstract Background and Aims Light chain cast nephropathy is the most common paraprotein-associated kidney lesion in patients with multiple myeloma (MM). Rarely, light chain cast nephropathy could show crystalline appearance in patients with multiple myeloma, also known as crystalline light chain cast nephropathy. We here report the first retrospective study of crystalline light chain cast from a single centre. Method All native kidney biopsies were retrospectively studied in the Peking University First Hospital from 2000 to 2020. Newly diagnosed MM patients with were enrolled. Patients with light chain cast nephropathy at least one cast with crystalline appearance were identified as crystalline light chain cast nephropathy (Figure 1, n = 8), others were identified as ordinary light chain cast nephropathy (n = 18). Results The cohort of crystalline light chain cast nephropathy consisted of 6 men and 2 women with a median age of 59.5 (range, 41-73) years. All patients suffered from advanced multiple myeloma (1 with ISS staging II, 7 with ISS staging III) and acute kidney injury with a median eGFR of 5.59 (range, 2.27-26.04) mL/min/1.73m2. All patients except 1 required emergency dialysis at admission. Microhematuria was presented in 3 patients. Median proteinuria was 2.13 (rang, 0.83-3.59) g/24h and median serum albumin was 38.2 (30.7-46.7) g/L. No one presented with nephrotic syndrome. Monoclonal immunoglobulin, detected in all patients on serum protein immunofixation electrophoresis, was λ alone in 5 patients, κ alone in 1 patient, IgG λ in 1 patient, IgA λ in 1 patient. The 8 patients were followed up with a median time of 8 (range, 2-24) months. Three patients received VAD chemotherapy and 5 patients received bortezomib based regimens. At the time of last follow-up, 2 of 7 patients who needed emergency dialysis got rid of dialysis and the rest remained dialysis-dependent. Five patients died with a median time of 5 (range, 2-19) months, 2 patients achieved partial remission and 1 patient achieved complete remission. There was no significant difference in clinical features, treatments and main outcomes between crystalline light chain cast nephropathy patients and ordinary light chain cast nephropathy patients (Table 1). However, crystalline light chain cast nephropathy patients had higher early mortality than ordinary light chain cast nephropathy patients (50.0% vs 11.1%, p = 0.03). Conclusion Crystalline light chain cast nephropathy patients usually presented with acute kidney injury requiring emergency dialysis. Although various types of monoclonal immunoglobulin were detected, there was a dominance of the λ isotype. Compared to ordinary light chain cast nephropathy patients, crystalline light chain cast nephropathy patients had higher early mortality.