Reduction Of Free Light Chains Research Articles

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.

#2634 ROLE OF LIGHT CHAIN CLEARANCE IN THE RECOVERY OF RENAL FUNCTION IN MULTIPLE MYELOMA: ANOTHER POINT OF VIEW

Abstract Background and Aims Acute Kidney Injury (AKI) in patients with multiple myeloma (MM) requiring renal replacement treatment (RRT) is associated with high morbidity and mortality. Early reduction of serum free light chains (FLC) using both targeted therapy against MM and intensive hemodialysis (IHD) may improve renal outcomes. We evaluated the effectiveness of two different RRT techniques on renal recovery in a MM patient population: standard dialysis procedure versus IHD with either PMMA or hemodiafiltration with endogenous reinfusion (HFR). Method Multicentric retrospective study with severe AKI related to MM, between 2011 and 2018. Twenty-five consecutive patients with AKI secondary of MM requiring RRT were included. Patients that underwent IHD received 6 dialysis sessions per week during the first 14 days (PMMA vs HFR). All patients were diagnosed with de novo MM or first relapsed MM. Primary outcome was renal recovery defined as dialysis-free at six months follow-up. Results A total of 25 patients were included. Seventeen patients received IHD and 8 standard dialysis. All patients were treated with targeted therapy, 84% bortezomib-based. Of the 25 patients included, fourteen (56%) became dialysis independent. We observed a higher proportion of patients who received IHD in the group who recovered kidney function compared to those who remained in HD (92.9% vs 36.4%, p:0.007). In our study, the use of IHD to remove FLC had a statistically significant association with renal recovery compared to standard dialysis group (p = 0.024). Conclusion Early reduction of FLC with IHD as an adjuvant treatment along with MM targeted therapy may exert a positive impact on renal recovery.

Role of light chain clearance in the recovery of renal function in multiple myeloma: another point of view.

Acute kidney injury (AKI) in patients with multiple myeloma (MM) requiring renal replacement treatment (RRT) is associated with high morbidity and mortality. Early reduction of serum free light chains (FLC) using both targeted therapy against MM and intensive hemodialysis (IHD) may improve renal outcomes. We evaluated the effectiveness of two different RRT techniques on renal recovery in an MM patient population: standard dialysis procedure vs IHD with either polymethylmethacrylate (PMMA) or hemodiafiltration with endogenous reinfusion (HFR). This was a multicentric retrospective study with severe AKI related to MM, between 2011 and 2018. Twenty-five consecutive patients with AKI secondary to MM requiring RRT were included. Patients that underwent IHD received six dialysis sessions per week during the first 14 days (PMMA vs HFR). All patients were diagnosed with de novo MM or first relapsed MM. Primary outcome was renal recovery defined as dialysis-free at 6 months follow-up. A total of 25 patients were included. Seventeen patients received IHD and eight standard dialysis. All patients were treated with targeted therapy, 84% bortezomib-based. Of the 25 patients included, 14 (56%) became dialysis independent. We observed a higher proportion of patients who received IHD in the group who recovered kidney function compared with those who remained in HD (92.9%vs 36.4%, P = .007). In our study, the use of IHD to remove FLC had a statistically significant association with renal recovery compared with the standard dialysis group (P=.024). Early reduction of FLC with IHD as an adjuvant treatment along with MM-targeted therapy may exert a positive impact on renal recovery.

Systematic Comparison of Uremic Toxin Removal Using Different Hemodialysis Modes: A Single-Center Crossover Prospective Observational Study

Many hypotheses could explain the mortality decrease observed using hemodiafiltration, such as reduction of intradialytic hypotension and more efficient toxin removal. We led a systematic analysis of representative uremic toxin removal with hemodialysis (HD), online postdilution hemodiafiltration (postHDF) and online predilution hemodiafiltration (preHDF), in a single-center crossover and prospective observational study. The primary outcome was the reduction ratio of uremic toxins of the three categories defined by the Eutox group. Twenty-six patients were treated by those three techniques of extra renal epuration. Mean Kt/Vurea was not different between the treatment methods. Mean reduction ratio of beta2microglobulin was significantly higher for both HDF treatments than for HD (p < 0.001). Myoglobin, kappa, and lambda free light chain reduction ratio was significantly different between the modes: 37.75 ± 11.95%, 45.31 ± 11% and 61.22 ± 10.56%/57.21 ± 12.5%, 63.53 ± 7.93%, and 68.40 ± 11.79%/29.12 ± 8.44%, 34.73 ± 9.01%, and 45.55 ± 12.31% HD, preHDF, and postHDF, respectively (p < 0.001). Mean protein-bound solutes reduction ratio was not different between the different treatments except for PCS with a higher reduction ratio during HDF treatments. Mean albumin loss was always less than 2 g. HDF improved removal of middle molecules but had no effect on indoles concentration without any difference between synthetic dialysis membranes.

Abstract CT186: Pharmacokinetic (PK) profile of a novel IKZF1/3 degrader, CFT7455, enables significant potency advantage over other IKZF1/3 degraders in models of multiple myeloma (MM) and the results of the initial treatment cohort from a first-in-human (FIH) phase 1/2 study of CFT7455 in MM

Abstract Introduction: CFT7455 is a highly potent and novel Ikaros Family Zinc Finger Protein 1/3 (IKZF1/3) degrader. In xenograft models, CFT7455 has more potent IKZF1/3 degradation compared to other degraders. Early observations from the FIH clinical trial (NCT04756726) along with supporting translational studies are presented here. Methods: Pre-clinical studies comparing CFT7455 and CC-92480 in both in vitro and xenograft models were performed. The pre-clinical studies’ results coincided with observations from the on-going clinical trial. The clinical trial is an open-label, Phase 1/2, multi-center, FIH study in heavily pretreated relapsed/refractory (R/R) MM and non-Hodgkin’s lymphoma (NHL) patients evaluating safety, tolerability, and PK of CFT7455. Eligible MM patients are R/R to therapy and are not candidates for regimens known to provide clinical benefit. A starting dose of 50 μg QD 21 days on/7 days off (21/7) in 28-day cycles was administered. Results: CFT7455 and CC-92480 showed similar cereblon binding profiles and in vitro IKZF1/3 degradation kinetics, translating into sub-nanomolar GI50 values in proliferation assays across a panel of MM cell lines. In the NCI-H929 xenograft model, 100 μg/kg/day of CFT7455 resulted in durable tumor regressions, while 1000 μg/kg/day of CC-92480 gave tumor stasis. Similar results were seen in a systemic model of MM, MM1.S. Both compounds achieved &amp;gt;95% IKZF3 degradation in tumors 4h post dose. At 48h post dose, CFT7455 was more effective than CC-92480 in maintaining IKZF3 degradation (65% vs. 6% respectively). When levels of CFT7455 and CC-92480 in plasma and tumor were compared, CFT7455 concentrations were &amp;gt; DC80 in tumor 48h post dose, while CC-92480 levels were undetectable in tumor and plasma, demonstrating CFT7455 has longer exposure resulting in sustained IKZF1/3 degradation in pre-clinical models. In cohort A, 5 heavily pre-treated MM patients (pts) received single agent CFT7455. 4 pts have received at least 3 cycles, with 2 pts receiving 5 cycles. Neutropenia (grade 4) was observed in 3/5 pts without coincident fever or infection. Additionally, a 2-4 fold accumulation in plasma CFT7455 exposure at steady state was observed. Early pharmacodynamic (PD) data demonstrates deep persistent degradation of IKZF3 (~100%) and serum free light chain reduction (up to 72%) in response to treatment. Stable disease has been observed in 34 pts, suggesting clinical benefit. Conclusions: While CFT7455 showed clinical benefit at 50 ug with deep target degradation, neutropenia was dose limiting. PK/PD modeling suggests alternative dosing regimens may result in increased tolerability with preserved efficacy, and evaluation of them is underway. Updated results will be presented at the meeting. Citation Format: Sagar Lonial, Shambavi Richard, Jeffrey V Matous, Andrew J. Yee, Urvi Shah, Neha Mehta-Shah, Thomas Martin, Eli Muchtar, Sikander Ailawadhi, Paul G. Richardson, Manisha Bhutani, Samantha Perino, Jason Kirby, Roman V. Agafonov, Prasoon Chaturvedi, Bradley Class, Matthew Schnaderbeck, Michael R. Palmer, Cathleen Gorman, Oliver Schoenborn-Kellenberger, Amanda Hoerres, Stewart L. Fisher, Roy M. Pollock, Adam Crystal, Michelle Mahler, Jesus Bardeja. Pharmacokinetic (PK) profile of a novel IKZF1/3 degrader, CFT7455, enables significant potency advantage over other IKZF1/3 degraders in models of multiple myeloma (MM) and the results of the initial treatment cohort from a first-in-human (FIH) phase 1/2 study of CFT7455 in MM [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT186.

MO889: High Flux Dialyzer 2.6 M2 is Promising for Free Light Chains Removal in High Flux Hemodialysis and Hemodiafiltration

Abstract BACKGROUND AND AIMS Immunoglobulin light chains are classified as middle molecule uremic toxins and its removal through effective dialyzer is needed with less albumin loss. This study assessed the free light chains removal using dialyzer surface area (SA) 2.6m2 in high flux dialysis (HD) versus hemodiafiltration (HDF) and its relation to cumulative albumin loss. METHOD A cross-over study included 25 patients who underwent hemodialysis using dialyzer surface area 2.6 m2 in high flux HD followed by online post-dilution hemodiafiltration with washout period 2 weeks using high flux dialyzers (max 2.0 m2 SA). All patients were subjected to single session measurement of dialysate albumin every hour and pre-post dialysis Free light chains (FLC) kappa and Lambda by ELISA. RESULTS Dialyzer (SA) 2.6m2 showed significant reduction in post-dialysis kappa and lambda in comparison to pre-dialysis level in high flux hemodialysis and hemodiafiltration (P &amp;lt; 0.001). HDF showed higher kappa and lambda FLC reduction ratio (45.16 ± 6.53 ng/mL), (28.68 ± 4.36 ng/mL), respectively compared with high flux HD (29.52 ± 6.38 ng/mL), (19.48 ± 1.96 ng/mL), respectively (P &amp;lt; 0.001). HDF/HD fold change of kappa and lamda were (1.56 ± 0.23) and (1.48 ± 0.26), respectively. Patients on HDF dialysis had significant total albumin loss in dialysate [median (IQR) 2.47 (1.16) gm/dL] compared with high flux dialysis [median (IQR) 0.65 (0.64) gm/dL] with (P &amp;lt; 0.001). Maximum albumin loss in patients on HDF was in the first hour [median (IQR) 1.22 (0.59)] gm/dL with lower albumin loss in the next hours reaching median {0.17 (0.15) gm/dL} in the fourth hour. Trans-membrane pressure was positively correlated with total albumin loss in high flux hemodialysis and hemodiafiltration (r 0.443, p 0.027, r 0.745, P = 0.001), respectively. CONCLUSION High flux dialyzer 2.6 m2 (SA) is effective for free light chains removal especially with online post-dilution hemodiafiltration with acceptable albumin loss.

ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI Expert Consensus Recommendations for Multimodality Imaging in Cardiac Amyloidosis: Part 1 of 2-Evidence Base and Standardized Methods of Imaging.

ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI Expert Consensus Recommendations for Multimodality Imaging in Cardiac Amyloidosis: Part 1 of 2-Evidence Base and Standardized Methods of Imaging.

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.

POS-604 MIDDLE MOLECULE CLEARANCE & EXPANDED DIALYSIS: WHAT IS THE IMPACT ON PATIENT-REPORTED SYMPTOM BURDE, THROUGH THE LENS OF THE LONDON EVALUATION OF ILLNESS (LEVIL)

Traditionally used high flux (HF) dialyzers are incapable of clearing toxins of larger middle molecular weight, which are mainly responsible for chronic systemic inflammation, cardiovascular adversity, and poor clinical outcomes in the hemodialysis (HD) population. The recent advent of medium cut-off dialyzers (MCO)–termed expanded dialysis (HDx), have been proven to clear these hard-to-reach toxins while selectively retaining valuable proteins–a step in the right direction as we strive to improve patient care. However, there is no literature focusing on the direct impact of HDx on patient-reported symptoms and quality of life (QoL); a mortality risk in itself. Historically used cross-sectional QoL and symptom measurement tools are unable to properly assess and track the variabilities of symptom burden and are not responsive to short-term changes. The London Evaluation of Illness (LEVIL) is a patient-reported symptoms measurement tool meant for iterative use, and captures fluctuations in real-time. Symptom domains measured by LEVIL include general well-being, energy, sleep quality, bodily pain, appetite, and breathing; domains relevant to the chronic kidney disease population. We report on the impact of 12 weeks of HDx therapy on symptom burden and QoL in patients undergoing conventional HD, measured by LEVIL. A single-centred interventional pilot study in the prevalent chronic HD population-London Health Sciences Centre where 22 participants completed the study. The study was 14 weeks in length; the first 2 weeks patients completed the LEVIL questionnaire with each dialysis session using their HF dialyzer to establish baseline symptom scores. Patients were then changed to Theranova (Baxter–MCO dialyzer) for 12-weeks, continuing the complete LEVIL with each HD session. Bloodwork for CBC, lytes, urea, Cr, Ca, Phos, Alb, CRP, B2M, Free-Light-Chains (FLC) were drawn at the beginning and end of the study. Baseline results were stratified into two groups. Those with an average baseline LEVIL score (scale of 0=poor, 100=excellent) of 70 or above were grouped as “HIGH baseline,” while those with a LEVIL score of <70 were labeled “LOW baseline.” When all six symptom domains were combined, resulting in an “overall” QoL score, 73% of patients had a LOW baseline score (mean 51.5±10.2). There was a significant improvement in overall QoL in this group after 8 (mean 64.6±16.2, p=0.0013) and 12 weeks of HDx therapy (mean 67.2±16.6, p=0.0001). There was no impact on overall QoL in those with a HIGH baseline score. There were no significant differences in lab values other than a reduction of FLC in both groups, most significantly in Kappa-FLC in those with LOW baseline scores (p=0.0182). Domain-specific results also showed that patients with LOW baseline scores benefited after 8 weeks of therapy in the domains of general well-being (p=0.0008) and energy (p=0.0011). Sleep quality improved after just 4 weeks of therapy (p=0.0098). HDx improves QoL and symptom burden in those with LOW baseline LEVIL scores, significantly impacting general well-being, energy, and sleep quality. LEVIL can identify patients who may benefit from HDx and proves to capture the response to treatment after 8 weeks in the domains that most significantly impact HD patients’ QoL. Could this be the ‘magic wand’ to improve patient care?

A Phase I Dose Escalation Study of PT-112 in Patients with Relapsed or Refractory Multiple Myeloma

Background: PT-112 is a novel pyrophosphate-platinum conjugate with a multi-modal mechanism of action that induces immunogenic cell death and is not susceptible to DNA-repair drug resistance pathways. In phase I studies in solid tumors, PT-112 demonstrated safety and efficacy as single agent and in combination with PD-L1 checkpoint inhibitor avelumab, crossing a range of dose levels (DL) and tumor types, including in heavily pre-treated patients (pts) non-responsive to immunotherapy and refractory to other modalities. Non-clinical, in vivo research using advanced imaging technology demonstrated that PT-112 reached the highest concentrations in bone tissue (osteotropism). Moreover, PT-112 was highly active in the orthotopic, immune-competent Vk*MYC mouse model of multiple myeloma, including drug-resistant transplant variants. Thus, a rationale for PT-112 as an investigational candidate in multiple myeloma was established. Here, we present results of a phase I dose escalation study of PT-112 in pts with relapsed or refractory multiple myeloma (RRMM). Methods: A 3+3 design was used to determine the recommended phase 2 dose (RP2D) for PT-112 (28-day cycle IV days 1, 8, 15) in pts with evaluable RRMM who had exhausted available therapies (Tx), with adequate bone marrow (abs neutrophil count ≥ 1.0 x 109/L; platelet count ≥ 50 x 109/L; and hemoglobin ≥ 8.0 g/dL) and renal function (calculated creatinine clearance ≥ 30 mL/min), and ECOG PS 0-2. Results: A total of 24 pts were treated with PT-112 monotherapy across 6 DLs: 125 mg/m2, 3 pts; 180 mg/m2, 4 pts; 250 mg/m2, 5 pts; 300 mg/m2, 4 pts; 360 mg/m2, 4 pts; 420 mg/m2, 4 pts. Patients had a median age of 72 years and were heavily pre-treated, with a median of 8 prior lines of systemic Tx: 22 (92%) pts were triple-class refractory with 19 (79%) pts penta-refractory, and 3 (13%) pts refractory to BCMA-based therapies. The most common treatment-related adverse events (TRAEs) were thrombocytopenia (58%), neutropenia (42%), diarrhea (38%), and nausea (38%). 38% of pts had ≥1 grade 3 non-hematologic TRAE, with no grade 4 non-hematologic TRAEs reported. One dose-limiting toxicity (DLT) of grade 4 neutropenia occurred at the 420 mg/m2 DL. In addition, due to frequent dose reductions and modifications at this DL, the safety committee declared 360 mg/m2 as the RP2D. Among 8 patients who received a starting dose at / above the RP2D, 2 had stable disease and 4 experienced responses to PT-112 Tx. These included a confirmed partial response (PR) achieved in a 79-year-old pt with kappa free light chain (FLC) disease treated at 360 mg/m2, whose previous Tx included combination regimens with most approved therapies (penta-refractory) and stem cell transplantation. FLC levels declined by 65% from baseline on PT-112 therapy and the pt remained progression free for 4.5 months. A 72-year-old pt treated at the 420 mg/m2 DL, reduced to 250mg/m2 every other week over the course of Tx due to grade 3-4 cytopenias, had a confirmed minor response. Prior Tx with multiple lines given over 9 years included stem cell transplantation, most approved therapies (penta-refractory), prior investigational antibody and CAR-T cell Tx (primary refractory to CAR-T). The patient was M-protein negative, kappa FLC levels declined by 32% following the first dose reduction, and the pt remained progression free and clinically stable without complaints for 4.5 months. Additionally, two transient, unconfirmed PRs occurred in patients at the 420mg/m2 DL: in a triple-class-refractory 82-year-old previously treated with 5 lines of Tx, with 70% reduction in kappa FLC during cycle 1; and in a penta-refractory 85-year-old, who experienced disappearance of M-protein during cycle 1 and Gr 4 neutropenia (DLT). Conclusions: PT-112 monotherapy was feasible and well tolerated in this heavily pre-treated, multi-refractory multiple myeloma population, and the Phase I clinical data appear to validate the developmental hypothesis, built upon activity in the Vk*MYC mouse model of multiple myeloma. Responses were confirmed in 25% of patients treated at / above the RP2D using single-agent PT-112, an encouraging result in a dose escalation trial conducted in heavily refractory patients. Activity of PT-112 in RRMM patients may be explained by its osteotropism and its unique mechanism of action compared to other drug classes used to treat this disease. Further clinical study of PT-112 in RRMM is warranted in a phase 2 clinical trial. Disclosures Ailawadhi: Celgene: Honoraria; Janssen: Research Funding; Pharmacyclics: Research Funding; Amgen: Research Funding; Medimmune: Research Funding; BMS: Research Funding; Cellectar: Research Funding; Phosplatin: Research Funding; Takeda: Honoraria. Vogl:Janssen: Consultancy; Celgene: Consultancy; MorphoSys: Consultancy; Takeda: Consultancy; Active Biotech: Consultancy, Research Funding; Oncopeptides: Consultancy; Karyopharm: Consultancy. Ames:Phosplatin Therapeutics: Current Employment, Current equity holder in private company. Yim:Phosplatin Therapeutics: Current Employment, Current equity holder in private company. Price:Phosplatin Therapeutics: Current Employment, Current equity holder in private company. Jimeno:Phosplatin Therapeutics: Current Employment, Current equity holder in private company.

Randomized Trial Comparing Double Versus Triple Bortezomib-Based Regimen in Patients With Multiple Myeloma and Acute Kidney Injury Due to Cast Nephropathy.

We report a multicenter controlled trial comparing renal recovery and tolerance profile of doublet versus triplet bortezomib-based regimens in patients with initial myeloma cast nephropathy (CN) and acute kidney injury (AKI) without need for dialysis. After symptomatic measures and high-dose dexamethasone, patients were randomly assigned to receive bortezomib plus dexamethasone (BD), or BD plus cyclophosphamide (C-BD). In patients with < 50% reduction of serum free light chains (sFLCs) after 3 cycles, chemotherapy was reinforced with either cyclophosphamide (BD group) or thalidomide (C-BD group). Ninety-two patients were enrolled in each group. At random assignment, characteristics of the 2 groups were similar, including median age (68 years) and serum creatinine level (305.5 and 273.5 µmol/L in BD and C-BD group, respectively). At 3 months, renal response rate (primary end point) was not different (41 v 47 responders in the BD and C-BD groups, respectively; relative risk [RR], 0.87; P = .46). Very good partial response (free light chain reduction ≥ 90%) or more was achieved in 36 and 47 patients, respectively (RR, 0.76; P = .10). After 1 cycle of chemotherapy, 69 in the BD group and 67 patients in the C-BD group had achieved sFLC level ≤ 500 mg/L. Serious adverse events were recorded in 30 and 40 patients, respectively. At 12 months, 19 patients had died (9 in the BD group v 10 in the C-BD group), including 10 (6 in the BD group and 4 in the C-BD group) from myeloma progression and 3 (0 in the BD group and 3 in the C-BD group) from infection. Within median follow-up of 27 months, 43 and 42 patients switched to new therapy, respectively. Overall, 50 patients (24 in the BD group and 26 in the C-BD group) had died. This randomized study did not show any benefit of C-BD compared with BD on renal recovery of patients with initial CN not requiring dialysis. Adding cyclophosphamide did not sufficiently improve the efficacy-toxicity balance. Patients with myeloma with AKI are fragile, and indication for doublet or triplet regimen should be adapted to frailty.

Hemodiafiltration with ultrafiltrate regeneration reduces free light chains without albumin loss in multiple myeloma patients

BackgroundAcute kidney injury (AKI) occurs in 12–20% of multiple myeloma (MM) patients. Several studies have shown a reduction of free light chains (FLC) using hemodialysis with High-Cut-Off membranes. However, this technique entails albumin loss. Hemodiafiltration with ultrafiltrate regeneration is a technique that includes a process of adsorption. The aim of this study was to evaluate the effectiveness of hemodiafiltration with ultrafiltrate regeneration in reducing FLC levels without causing albumin loss.MethodsThis is an observational study (2012 to 2018) including nine patients with MM (5 kappa, 4 lambda) and AKI. All patients were treated with chemotherapy and hemodiafiltration with ultrafiltrate regeneration. Blood Samples (pre and post-dialysis) and ultrafiltrate were collected pre and post-resin at 5 min after initiation of the session and 5 min before the end of the procedure.ResultsThe serum levels of kappa and lambda were reduced by a 57.6 ± 10% and 33.5 ± 25% respectively. Serum albumin concentration remained unchanged after the procedure. In the ultrafiltrate, the mean FLC reduction ratio shortly after initiation of the dialysis procedure was: 99.2 and 97.06% for kappa and lambda respectively, and only 0.7% for albumin; and at the end of the session the percent reduction was: 63.7 and 33.62% for kappa and lambda respectively, and 0.015% for albumin. Patients clinical outcome was: 33.3% recovered renal function, 22.2% died during the first year and 44.4% required maintenance dialysis.ConclusionsHemodiafiltration with ultrafiltrate regeneration reduces FLC levels without producing a significant loss of albumin; and, FLC removal is maintained throughout the session. Therefore, hemodiafiltration with ultrafiltrate regeneration may be considered an effective adjunctive therapy in patients with MM.

P1082COMPARISON OF THE REMOVAL OF PROTEIN-BOUND TOXINS AND LARGE MIDDLE MOLECULES WITH HIGH-FLUX PMMA AND MEDIUM CUT-OFF DIALYZERS

Abstract Background and Aims Dialytic clearance of protein-bound toxins and large middle molecules is poor by diffusive treatment and limited by high-flux hemodialysis (HD) and on-line hemodiafiltration (OL-HDF), and only a few studies have examined how to improve their removal by other extracorporeal strategies. Since 2017, there is a new generation of polymethyl methacrylate (PMMA) membranes that suppress platelet adhesion on the membrane surface improving hemocompatibility and permeability, while also maintaining adsorption properties related to conventional PMMA membranes. Expanded HD (HDx) with medium cut-off (MCO) membranes has also recently been incorporated into clinical practice and may improve the removal of uremic toxins in HD treatments. The aim of this pilot study was to compare the efficacy of a new high-flux PMMA dialyzer (Filtryzer® NF-2.1H) in a post-dilution OL-HDF session with a new MCO membrane (Theranova® 400) in a HDx session. Method In an open, cross-over, single-center, controlled, prospective clinical study, 40 adult stable HD patients were assigned to be treated by post-dilution OL-HDF with the NF-2.1H dialyzer or by HDx with the Theranova 400 dialyzer. All other dialysis parameters, including blood and dialysate flow rates, length of dialysis session, and ultrafiltration rate remained unchanged during both sessions. P-cresyl sulfate (PCS), indoxyl sulfate (IS), and kappa (κ) and lambda( λ) free light chains (FLC) reduction rates were intraindividually compared for the two dialyzer types (primary outcomes). Secondary outcomes included the kt and the reduction ratio of blood urea nitrogen, phosphate and β2 -microglobulin (β 2-m). Results The reduction ratio of protein-bound toxins ranges from 60% to 67%, with no differences between membranes (Figure). PMMA membrane achieved greater FLC reduction ratios than MCO membrane, reaching significance for λFLC (56.6% vs. 77.4%; p &amp;lt; 0.001). Conversely, β2M reduction ratio was slightly but significantly higher with MCO membrane (68.5 vs. 72.1%; p = 0.002). Small molecules removal including urea and phosphate were similar in both groups, achieving an optimal Kt with no differences between groups (61.3±9.2 Vs. 59.7±9.3; p=0.16). Albumin reduction ratio tended to be higher with PMMA membrane without reaching significance (10.1±5.9% Vs. 7.8±12.3%; p=0.17). The mean convective volume achieved with PMMA was 23.5±4.4 L. Conclusion This study suggested that new high-flux PMMA dialyzer in post-dilution OL-HDF mode might achieve better FLC reduction ratios than MCO dyalizer in HDx mode, whereas both techniques may equally remove protein-bound toxins. OL-HDF with new PMMA membranes could be a good dialysis strategy for adding convective transport to the well-known mechanisms of diffusion and absorption previously described with conventional PMMA membranes, enabling an adequate substitution volume.

Biomarkers of minimal residual disease in rituximab-treated patients with mixed cryoglobulinemia.

Hepatitis C virus (HCV) represents the major risk factor for mixed cryoglobulinemia (MC), a small-vessel vasculitis that may evolve into an overt B-cell non-Hodgkin's lymphoma. Here, we aimed to identify a biomarker signature for the early diagnosis of minimal residual disease (MRD). We assessed free light chains (FLCs), IgM k,and IgM λ heavy/light chain (HLC) pairs, and vascular endothelial growth factor (VEGF) in sera from 34 patients with MC vasculitis (32 HCV- and 2 HBV-related), treated with low-dose rituximab (RTX). FLCs and IgM HLCs were measured by turbidimetric assay; VEGF by an enzyme-linked immunosorbent assay. After RTX, the positive (complete+partial) clinical and laboratory responses were of 85.29% and 50%, respectively; in contrast, the mean levels of FLCs, IgM HLCs, and VEGF were substantially unaffected in most patients and still above the normal range. In those achieving a reduction of FLCs and IgM k and λ chains values within the range of normality, we found that post-treatment free λ chains and IgM k values correlated with clinical and laboratory response. Our results suggest that high levels of FLCs, IgM HLCs, and VEGF could represent the signature of "dormant" B cell clones' activity that could be very useful to identify MRD indicative of possible relapse or worsening outcome.

Abatacept induced long-term non-progressive reduction in gamma-globulins and autoantibodies: dissociation from disease activity control.

To evaluate long-term effects on gamma-globulins and autoantibodies of abatacept (ABA) versus tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients. Eighteen RA patients undergoing abatacept (ABA-RA) and 18 age/sex-matched patients treated with TNFi (TNFi-RA) were compared regarding clinical data, total gamma-globulins (TGG), specific subtypes (IgG, IgM, IgA), free light chains (FLC), IgM/IgG rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP3), and anti-mutated citrullinated vimentin (anti-MCV), assessed before and every 6months, up to 24months. previous abatacept/rituximab or low TGG (< 0.7g/dL). At baseline, female sex (78 vs. 78%), age (55 vs. 53years), DAS28 (5.73 vs. 5.67), TGG (1.4 vs. 1.35g/dL), IgG (1168 vs. 1079mg/dL), IgM (107 vs. 113mg/dL), IgA (333 vs. 322mg/dL), kappa (342 vs. 249mg/dL), lambda (170 vs. 150mg/dL), IgM-RF (76 vs. 53UI), IgG-RF (63 vs. 25UI), anti-CCP3 (216 vs. 189UI), and anti-MCV (202 vs. 102UI) were comparable in ABA-RA and TNFi-RA (p > 0.05). Similar disease activity improvement was observed in both groups. In ABA-RA, significant decreases (p < 0.05) were observed in TGG (1.4 vs. 1.05g/dL), IgG (1168 vs. 997), IgA (333 vs. 278mg/dL), kappa (342 vs. 257mg/dL), lambda (170 vs. 144mg/dL), IgM-RF (76 vs. 37UI), IgG-RF (65 vs. 24UI), anti-CCP3 (216 vs. 183UI), and anti-MCV (202 vs. 60UI) at 6months, without further decreases. In contrast, TNFi-RA showed no decrease in any of such parameters. ABA-RA also had more often transient IgG levels under the lower limit of normality (66.7% vs. 33.3%, p = 0.046). No severe infection occurred. DAS28, ESR, and CRP correlated significantly to gamma-globulins and FLC at baseline (p < 0.05), but these correlations were longitudinally lost in ABA-RA, but not in TNFi-RA. ABA, but not TNFi, induces a safe, persistent, long-term, and non-progressive reduction in gamma-globulins and autoantibodies, including anti-MCV. This pattern is dissociated from disease activity control.Key Points• ABA induces a long-term and non-progressive reduction in gamma-globulins and FLC, which occurs regardless of disease activity control.• ABA-induced reduction in gamma-globulins and FLC promotes a dissociation of such parameters and disease activity.• The same pattern of reduction is observed in autoantibodies: IgM-RF, IgG-RF, anti-CCP3, and anti-MCV.• Low transient IgG can be observed in RA patients treated with ABA, but does not correlate to infection.

The Quest for Indicators of Profound Hematologic Response in AL Amyloidosis: Complete Response Remains the Optimal Goal of Therapy

Background: The International Society of Amyloidosis validated the criteria of hematologic response to therapy in AL amyloidosis, based on the reduction of free light chain (FLC) concentration and serum and urine immunofixation. Complete response (CR) predicted the longest survival and was defined by negative serum and urine immunofixation (s&amp;u-IFE) with a normal FLC ratio (FLCR). Subsequently, we and others showed that, in patients with a difference between involved and uninvolved FLC (dFLC) between 20 and 49 mg/L, achieving a dFLC &lt;10 mg/L was associated with an improvement of overall and renal survival. This criterion was then proposed as a goal of therapy in the general population of patients with AL amyloidosis. These studies questioned whether the definition of CR should be reconsidered. In the present study, we compared the outcome of patients who obtained a profound reduction of FLC but do not qualify for CR with the outcome of subjects who reached CR. Methods: The prospectively maintained database of the Pavia Amyloidosis Center was searched for patients who were newly-diagnosed between 2004 and 2018 and who reached at least one the following endpoints 6 months after treatment initiation: 1) complete response (CR) or, in patients who do not qualify for CR, 2) normalization of involved-FLC concentration (normal-iFLC group), dFLC &lt;10 mg/L (dFLC10 group) and normalization of FLCR (normal-FLCR group). We calculated overall survival (OS) and time to next line of therapy or death (TNTD) from the time of response assessment (6 months after treatment initiation). Results: A total of 434 patients (Table) were included, that were divided into the following groups: CR (161), normal-iFLCN (114), dFLC10 (144) and normal-FLCR (220). As expected, there was a partial overlap between the non-CR groups. No difference was seen between the CR and all the other groups in baseline variables: age, sex, organ involvement, Mayo 2004/European staging, and renal staging. Treatment was bortezomib-based in 261 subjects, melphalan/dexamethasone (MDex) in 128, IMiDs-based in 21, autologous stem cell transplant in 14, and therapy for IgM clones in the remaining 10 subjects. The reasons for not qualifying for CR in the normal-iFLC group was abnormal FLCR only in 4 (3%), positive s&amp;u-IFE only in 81 (72%), and both in 29 (25%). The reason for not qualifying for CR in the dFLC10 group was abnormal FLCR only in 4 (3%), positive s&amp;u-IFE only in 104 (72%) and both in 36 (25%). The median follow-up of living patients was 60 months. Patients who achieved CR enjoyed a significantly longer OS (58% alive at 10 years) compared to patients who reached any of the other endpoints but did not qualify for CR (Figure). Also median TNTD was significantly longer in patients who obtained CR (75 months) compared to the normal-iFLC group (33 months, P&lt;0.001), the dFLC10 group (39 months, P&lt;0.001), and the normal-FLCR group (24 months, P&lt;0.001). We then evaluated whether achieving a normal iFLC or a dFLC &lt;10 mg/L was associated with a better survival among patients who did qualify for CR. In the CR group, 103 (64%) patients achieved a normal iFLC and 86 (53%) a dFLC &lt;10 mg/L. There was no significant difference in OS and TNTD between subgroups of patients in CR according to iFLC or dFLC response. Conclusion: Undetectable clonal disease by both negative serum and urine IFE and normal FLCR (CR) is associated with best survival in AL amyloidosis and should be the goal of therapy if tolerability and patient frailty allow. However, it is possible that novel immunotherapies, such as daratumumab, affect the concentration of uninvolved FLC, thus interfering with dFLC and FLCR, and this study should be validated in patients exposed to these agents. Approximately 40% of patients in CR relapse and eventually die. New sensitive tools to identify residual clonal disease (mass-spectrometry on serum and urine, next generation sequencing and next generation flow cytometry on bone marrow) are urgently needed to detect these patients and intervene before relapse. Disclosures Milani: Janssen: Honoraria; Pfizef: Honoraria. Palladini:Janssen-Cilag: Other: Travel grant; Janssen-Cilag: Honoraria; Celgene: Other: Travel grant; Sebia: Honoraria.

Erythropoietin Level and Percentage of Urinary Albumin Are Important for Renal Recovery in Patients with Multiple Myeloma Receiving Novel Agents

BackgroundRenal impairment (RI) is one of the most common complications of multiple myeloma (MM), and is a major cause of morbidity and mortality. Monoclonal free light chain (FLC) is associated with most RI in patients with MM, and previous reports showed that early reduction of FLC is associated with renal recovery. Novel agents including bortezomib and immunomodulatory drugs (IMiDs) contribute to early reduction of FLC, leading to renal recovery. However, some patients developed irreversible RI despite the use of novel agents, and the factors that predict renal recovery other than early reduction of FLC remain unclear. This study retrospectively analyzed the clinical variables that affect renal recovery in patients with RI receiving novel agents.Patients and MethodsThe study population consisted of 235 consecutive patients with newly diagnosed MM (NDMM) between January 2008 and April 2018 at Kameda Medical Center, Japan. All patients were treated with bortezomib or IMiD-based combined chemotherapy in the frontline setting. Nine patients who received less than 2 courses of chemotherapy were excluded because it was difficult to assess renal recovery. RI was defined as an estimated pretreatment glomerular filtration rate (eGFR) of <50 ml/min/1.73 m2. We used the simplified Modification of Diet in Renal Disease formula to calculate eGFR. Maximum renal response was evaluated according to International Myeloma Working Group (IMWG) renal response criteria. Major renal response was defined as achieving PRrenal and CRrenal. Erythropoietin (EPO) was measured, if a patient had anemia (male: hemoglobin [Hb] <12.0 g/dl, female Hb <11.0 g/dl). Statistical analyses were performed with EZR, which is a graphical user interface for R ver. 3.2.2.Ethical considerationsThis study was approved by the institutional review board of Kameda Medical Center and conducted in accordance with the principles of the Declaration of Helsinki.ResultsThe median patient age was 72.2 years and the median observation period was 40.8 months. Moderate-to-severe RI (eGFR <50 mL/min/1.73 m2) was identified in 104 patients (46.5%). The median eGFR was 27.9 ml/min/1.73 m2. The percentage of patients with light-chain only isotype was 28.8%, and 57.7% of the patients had kappa light chain. According to IMWG renal response criteria, 54.8% of patients achieved major renal response, including PRrenal 4.8% and CRrenal 49.0%. Baseline involved FLC, reduction of FLC, light chain-only isotype, and kappa light chain type were not statistically significant between patients with or without major renal response. There were significant differences in age, calcium, EPO, and percentage of urinary albumin excretion between responders and non-responders (Table). Receiver operating characteristic curve analysis showed that the best cutoff values were 24.6 mIU/ml for EPO and 24.7% for the percentage of urinary albumin (Figure). The factors associated with major renal response included age <75 years, calcium, percentage of urinary albumin <25%, and EPO ≥25 mIU/ml. The multivariate logistic regression analysis showed that age <75 years [Odds ratio (OR)=9.86; p=0.005], calcium (OR=8.94; p=0.010), percentage of urinary albumin <25% (OR=15.5; p=0.002), and EPO ≥25 mIU/ml (OR=18.4; p<0.001) were independent predictive factors for renal recovery. When patients were divided based on the percentage of urinary albumin <25% and level of EPO ≥25 mIU/ml, the proportion of those who achieved major renal recovery was significantly different among 3 groups (both urinary albumin <25% and EPO ≥25 mIU/ml vs. either urinary albumin <25% or EPO ≥25 mIU/ml vs. neither urinary albumin <25% nor EPO ≥25 mIU/ml: 84.2% vs 32.3% vs. 6.0%, p<0.001).ConclusionOur results indicate that early reduction of FLC could have less predictive value for renal recovery compared to that in previous reports because early FLC reduction could be obtained in almost all patients irrespective of improvement in renal function. However, the level of serum EPO and the percentage of urinary albumin emerged as positive predictive factors for renal recovery in patients with RI receiving novel agents. The combination of these 2 variables could predict renal recovery more precisely. DisclosuresNo relevant conflicts of interest to declare.

Increasing Daratumumab Frequency As a Way to Restore Responses- a Retrospective Case Study

Introduction:Multiple Myeloma (MM) remains difficult to treat despite significant advances in treatment options. Daratumumab (dara) as a single-agent or in combination with other treatments has considerable efficacy even among patients with highly-refractory disease. However, nearly all patients will fail dara. Dara frequency decreases throughout the treatment, from weekly eventually to monthly dosing, which may in part contribute to relapse. It has been hypothesized that increasing the frequency of dara may help restore responses in patients progressing on dara, but little data exists.Methods:In this retrospective case study, we identified 5 patients from our clinical database who received standard dara (weekly for 2 cycles, every other week for 4 cycles, then monthly thereafter) as a single agent or in combination, who had frequency re-escalated at relapse in attempt to recapture response.Results:Patient 1 is a 67 yo male with quad-refractory MM who received single-agent dara. He had a PR following 1 cycle but disease plateaued, ultimately progressing with rising M-protein following cycle 7 of treatment. Dara frequency was re-escalated to once weekly and the patient once again obtained a PR following the first cycle. The patient received 2 additional cycles at which time he had further evidence of PD and was switched to alternative treatment.Patient 2 is a 68 yo female with quad-refractory MM who received single-agent dara. She had a PR following 1 cycle but disease plateaued, ultimately progressing with rising free-light chains following cycle 12 of treatment. Dara frequency was re-escalated to once every other week. The patient had a mild reduction free-light chains (not meeting PR) and went on to receive 8 additional cycles before having further evidence of PD and switching to supportive care only.Patient 3 is a 73 yo male with refractory MM who received dara in combination pomalidomide (pom) and dexamethasone (dex). The patient had previously progressed on pom/dex. He had a PR following 2 cycles but disease plateaued, ultimately progressing with rising free-light chains following cycle 8 of treatment. Dara frequency was re-escalated to once weekly. The patient had a mild reduction in free-light chains (not meeting PR) and went on to receive 5 additional cycles before having further evidence of PD and switching to alternative treatment.Patient 4 is a 68 yo male with refractory MM who received single-agent dara. He had a PR following 1 cycle, and a VGPR following cycle 3. The patient later progressed following 14 cycles with rising M-protein and new lesion requiring XRT. Dara frequency was re-escalated to once weekly. The patient had a mild reduction M-protein (not meeting PR) and went on to receive 8 additional cycles before having further evidence of PD and switching to alternative treatment.Patient 5 is a 69 yo female with refractory MM who received dara/pom/dex. She was previously naïve to pom. The patient initially had stable disease but progressed with increasing free-light chains following cycle 6. Dara frequency was re-escalated to once weekly. The patients free-light chains returned to baseline levels and she went on to receive an additional 5 cycles before having further evidence of PD and switching to alternative treatment.Conclusion:Increasing dara frequency, can result in stabilization or improvement of myeloma disease markers in patients who were previously relapsing. This strategy may be clinically beneficial to patients who are showing signs of early biochemical progression but are otherwise doing well. Prospective trials are warranted to further evaluate this approach. DisclosuresVickroy:Amgen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Bristol-Meyers Squibb: Honoraria, Speakers Bureau. Peery:Novartis: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Schroeder:Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vij:Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Light Chain Cast Nephropathy: Practical Considerations in the Management of Myeloma Kidney-What We Know and What the Future May Hold.

To update and evaluate the current knowledge on pathogenesis and management of light chain cast nephropathy. Light chain cast nephropathy (LCCN) is the leading cause of acute renal failure in patients with multiple myeloma and is currently recognized as a myeloma defining event. The immunoglobulin free light chain plays an integral role in the pathogenesis of LCCN. The level of free light chain (FLC) in the blood and urine is directly associated with the risk of developing LCCN. Recovery of renal function is related to the speed and degree of the serum FLC reduction. Recently, two randomized trials using high cutoff dialyzer for the removal of serum FLC produced different results in terms of renal recovery. FLC plays a key role in the development and resolution of LCCN. Future therapies will aim to rapidly reduce its concentration or interrupt its interaction with Tamm-Horsfall protein.

Serum Free Light Chains Removal by HFR Hemodiafiltration in Patients with Multiple Myeloma and Acute Kidney Injury: a Case Series

Background/Aims: Multiple myeloma (MM) represents 10% of all haematologic malignancies. Renal involvement occurs in 50% of MM patients; of them, 12-20% have acute kidney injury (AKI), with 10% needing dialysis at presentation. While hemodialysis (HD) has no effect upon circulating and tissue levels of monoclonal proteins, novel apheretic techniques aim at removing the paraproteins responsible for glomerular/tubular deposition disease. High cut-off HD (HCO-HD) combined with chemotherapy affords a sustained reduction of serum free light chains (FLC) levels. One alternative technology is haemodiafiltration with ultrafiltrate regeneration by adsorption on resin (HFR–SUPRA), employing a “super high-flux” membrane (polyphenylene S-HF, with a nominal cut-off of 42 kD). Aim of our pilot study was to analyze the effectiveness of HFR-SUPRA in reducing the burden of FLC, while minimizing albumin loss and hastening recovery of renal function in 6 subjects with MM complicated by AKI. Methods: Six HD-dependent patients with MM were treated with 5 consecutive sessions of HFR-SUPRA on a Bellco® monitor, while simultaneously initiating chemotherapy. Levels of albumin and FLC were assessed, calculating the rates of reduction. Renal outcome, HD withdrawal and clinical follow-up or death were recorded. Results: All patients showed a significant reduction of FLC, whereas serum albumin concentration remained unchanged. In three, HD was withdrawn, switching to a chemotherapy alone regimen. The other patients remained HD-dependent and died shortly thereafter for cardiovascular complications. Conclusion: Our study suggests that HFR-SUPRA provides a rapid and effective reduction in serum FLC in patients with MM and AKI, while minimizing the loss of albumin. When started early in combination with chemotherapy, blood purification by HFR-SUPRA was followed by the recovery of renal function in half of the patients treated.