Abnormal Serum Free Light Chain Research Articles

Intracapillary monoclonal IgM deposits disease with massive pseudothrombi: A clinicopathologic study of 4 cases and literature review.

Intracapillary monoclonal IgM deposits disease (ICMDD) has long been considered a hallmark of Waldenström macroglobulinemia (WM) nephropathy. Intracapillary immunoglobulin thrombi are the characteristic features of cryoglobulinemic glomerulonephritis. Here, we reported 4 cases of ICMDD with massive pseudothrombi but without WM or cryoglobulinemia. We retrospectively analyzed the clinical and pathologic features of patients diagnosed with ICMDD with massive pseudothrombi. A total of 4 patients (2 men and 2 women) aged 62 to 73 years were enrolled in this study. Microscopic hematuria, edema, and renal insufficiency were present in all patients, along with low serum C3 and C4 in 2 patients. Hematologic examination showed abnormal serum free light chain ratios in all patients and high levels of serum IgM in 3 patients. IgM-κ monoclonal band was identified by serum immunofixation electrophoresis in 3 patients. One patient was diagnosed with small B-cell lymphoma by bone marrow aspiration. Renal biopsy specimen showed massive periodic acid-Schiff-positive hyaline thrombi in the glomerular capillary lumens and also less mesangial, subendothelial, and subepithelial deposits on light microscopy. Immunofluorescence indicated positive staining for IgM (++) and κ light chain staining in the glomerular capillary lumens, capillary walls, and mesangium in all patients. By electron microscopy, the glomerular capillary lumens were filled with homogeneous high-electron-dense deposits without substructure. Two patients were treated with prednisone combined with cyclophosphamide, and 2 received plasma cell-targeted chemotherapy. One patient achieved partial renal remission. Intracapillary monoclonal IgM deposits disease is a rare disease and not always related to WM. Most patients have IgM monoclonal immunoglobulinemia; renal biopsy specimens mainly show a large number of pseudothrombi in the glomerular capillary lumens. Cyclophosphamide is effective in some patients.

Serum-free light chain test utilisation at a South African academic laboratory and comparison with serum protein electrophoresis results.

Serum protein electrophoresis (SPE), urine protein electrophoresis and immunofixation electrophoresis were traditionally utilised for the diagnosis of monoclonal gammopathies. The quantitative serum-free light chain (SFLC) assay is reportedly more sensitive and has been introduced to recent clinical guidelines. This study aimed to investigate SFLC test utilisation and describe SPE findings in patients with abnormal SFLC ratios. A retrospective audit of SFLC analyses was conducted in Cape Town, South Africa, from May 2018 to April 2020. Agreement between abnormal SFLC ratios and SPE results was determined in a sub-group of patients screened for monoclonal gammopathies. Serum-free light chains were analysed using Freelite® Kappa and Lambda assays. Of the 1425 patients included in the audit, 741 (52%) had abnormal SFLC ratios; 636 (45%) had increased and 105 (7%) had decreased SFLC ratios. In a sub-group analysis of 117 new patients with an abnormal SFLC ratio, 57 had a monoclonal protein (M-protein) on SPE (49%), and 60 (51%) did not. Four out of 60 patients without M-protein had a plasma cell dyscrasia, while renal impairment or inflammatory response accounted for the rest. Of the 57 patients with a M-protein and abnormal SFLC ratio, 41 (72%) had a plasma cell dyscrasia, seven (12%) had lymphomas and nine patients (16%) were unclassifiable. Serum-free light chains should be requested when there is a high index of clinical suspicion. Neither SFLC nor SPE should be performed in isolation when screening patients for monoclonal gammopathy, to ensure that no patient is missed. The study adds to the evidence on SFLC test utilisation. Serum protein electrophoresis alone may miss cases of light chain myeloma, while SFLC performed in isolation may produce false positive results in the setting of inflammatory disorders or renal impairment, leading to unnecessary further investigation.

The electrophysiological substrate of biopsy-proven cardiac amyloidosis

Abstract Background Cardiac amyloidoses (CA) are an increasingly recognized group of infiltrative cardiomyopathies associated with high risk of major adverse cardiac events. Endomyocardial biopsy (EMB) may be required to differentiate the amyloid type (mainly, Immunoglobulin light chain [AL] versus transthyretin-related [ATTR]) in some cases. Purpose The aim of this study was to provide the first description of the right ventricular (RV) electroanatomical substrate of CA, and assess its association with EMB findings and clinical outcomes. Methods We enrolled ten consecutive patients undergoing EMB for suspected CA (median age, 68[63-77]; male, 50%) in a monocentric, observational, retrospective study. All patients had a clinical diagnosis of CA, but a diagnosis of CA type was hampered by the presence of inconclusive or discordant laboratory-imaging findings (abnormal serum free light chain assay and positive bone scintigraphy, n=5; ambiguous imaging results, n=4; abnormal serum free light chain assay and TTR gene mutation, n=1). Therefore, each patient underwent RV high-density electroanatomical voltage mapping (EVM) and EMB. The primary outcome was death or hospitalization at 1-year follow-up. We recorded electrogram features at EMB sampling sites and in the overall RV, and explored their correlations with histopathological findings and primary outcomes events. Results A final EMB-proven diagnosis of AL or ATTR CA was formulated in 6 and 4 patients, respectively. Electrogram amplitudes in the bipolar and unipolar configurations averaged 1.58±0.65 mV, and 5.38±1.41 in the overall RV. We found a significant inverse correlation between unipolar electrogram amplitude and amyloid burden at EMB (p<0.001); the unipolar voltage cutoff that best identified regions with >15% amyloid tissue infiltration according to Youden index was 9.1 mV (sensitivity, 43%; specificity, 100%; accuracy, 77%). At 1-year follow-up, 6 patients (60%) experienced a primary outcome event. Compared to subjects with uneventful follow-up, patients with a primary outcome event had larger unipolar low-voltage zones (32.3 [6.1] cm2 vs. 20.7 [6.5] cm2, p=0.043) and bipolar dense scar areas (6.1 [2.3] cm2 vs. 1.8 [0.7] cm2, p=0.005), and after pooling mapping points from all patients, unipolar electrogram amplitude was moderately associated with primary outcome events (AUC: 0.65 [95% CI, 0.64-0.65]). Conclusions In CA, electrogram amplitudes are around the lower limit of normal, yet disproportionately low compared to the increased wall thickness. We found evidence that unipolar electrogram amplitude may be a quantitative marker of amyloid burden, possibly associated with adverse clinical outcomes.EVM and EMB in ATTR cardiac amyloidosisEVM and EMB in AL cardiac amyloidosis

Impact of cytogenetic abnormalities on the risk of disease progression in solitary bone plasmacytomas

AbstractMost patients with solitary bone plasmacytomas (SBP) progress to multiple myeloma (MM) after definitive radiation therapy as their primary treatment. Whether the presence of high-risk (HR) cytogenetic abnormalities by fluorescence in situ hybridization (FISH) in the clonal plasma cells, obtained either directly from the diagnostic SBP tissue or the corresponding bone marrow examination at the time of diagnosis, is associated with a shorter time to progression (TTP) to MM is unknown. This study evaluated all patients diagnosed with SBP at the Mayo Clinic from January 2012 to July 2022. The presence of del(17p), t(14;16), t(4;14), or +1q (gain or amplification) by FISH in clonal plasma cells was defined as HR. A total of 114 patients were included in this cohort, and baseline FISH was available for 55 patients (48%), of which 22 were classified as HR (40%). The median TTP to MM for patients with SBP and HR FISH was 8 months (95% confidence interval [CI], 6.3-26) compared with 42 months (95% CI, 25-not reached [NR]) in patients with SBP without HR FISH (P < .001). In a multivariate analysis, only HR FISH was a significant predictor for shorter TTP to MM, independent of minimal marrow involvement and an abnormal serum free light chain ratio at diagnosis. Deletion (17p) and gain 1q abnormalities were the most common FISH abnormalities responsible for the short TTP to MM. Thus, assessing for HR FISH abnormalities in clonal plasma cells derived from either the diagnostic SBP tissue or the staging bone marrow examination of patients with newly diagnosed SBP is feasible and prognostic for a shorter TTP to MM.

Electroanatomical features of biopsy-proven cardiac amyloidosis

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac amyloidoses (CA) are an increasingly recognized group of infiltrative cardiomyopathies associated with high risk of heart failure, thromboembolic events, arrhythmias, and sudden death. Endomyocardial biopsy may be required to differentiate the amyloid type (mainly, Immunoglobulin light chain [AL] versus transthyretin-related [ATTR]) in some cases. Purpose to provide a first description of electroanatomical characteristics of amyloid cardiomyopathy, and relate them to endomyocardial biopsy findings. Methods we enrolled ten consecutive patients (median age, 68 [63-77]; male, 50%) in an observational, retrospective study. All of them had a clinical diagnosis of CA, but a diagnosis of CA type was hampered by the presence of inconclusive or discordant laboratory-imaging findings (abnormal serum free light chain assay and positive bone scintigraphy, n=5; ambiguous imaging results, n=4; abnormal serum free light chain assay and TTR gene mutation, n=1). Therefore, all patients underwent right ventricular high-density electroanatomical mapping (EAM) using a multipolar catheter (Advisor HD Grid, Abbott), and EAM-guided endomyocardial biopsy (EMB). We recorded electrogram features at EMB sampling site, and explored their correlation with histological findings with mixed effect models. Results The clinical, electroanatomical, and histological features of enrolled patients according to the EMB-proven type of CA (AL, n=6; ATTR, n=4) are resumed in Table. Electrogram amplitudes in both the bipolar and the unipolar configuration were generally normal both in the overall right ventricle, and at EMB sites. We found a significant correlation between both unipolar and bipolar electrogram amplitude and the percentage of both amyloid tissue (p&amp;lt;0.01 and p=0.016, respectively) and fibrous tissue (both p&amp;lt;0.01) at EMB (Figure). We observed the strongest linear association (i.e., highest R2) between unipolar electrogram amplitude and amyloid tissue, as well as between bipolar electrogram amplitude and fibrous tissue. On the other hand, electrogram duration and the number of electrogram peaks were unrelated to histological findings. The unipolar voltage cutoff that best identified regions with &amp;gt;15% amyloid tissue infiltration according to Youden index was 9.1 mV (sensitivity, 43%; specificity, 100%; accuracy, 77%). Conclusion CA is associated with normal electrogram amplitudes using ahigh density mapping catheter and conventional voltage cutoffs. Nevertheless, unipolar electrogram amplitude is strongly related to the extent of amyloid infiltration, and unipolar voltage&amp;lt;9.1 mV is 100% specific for &amp;gt;15% amyloid tissue deposition.

Immunophenotypic expression profile of multiple myeloma cases at a tertiary hospital in Nairobi Kenya.

Multiple myeloma (MM) is a plasma cell neoplasm that constitutes 10-15% of all hematopoietic neoplasms. Kenya is placed among the top five African countries for MM incidence and MM-related mortality. Prior studies have suggested that the aberrant expression of Cyclin D1, CD56, CD117 and Ki-67 on neoplastic plasma cells is useful in disease prognostication. The prevalence and significance of expression of these markers in a cohort of MM cases in Kenya has not been studied previously. A retrospective cross-sectional study was carried out at the Aga Khan University Hospital, Nairobi. The study population included 83 MM cases with available trephine blocks archived between 1st of January 2009 and 31st of March 2020. Immunohistochemical expression of Cyclin D1, CD56, CD117, and Ki-67 was analyzed and scored. The biomarkers were described using frequencies based on the positive and negative results. Fisher's exact test was used to determine the association between the immunophenotypic markers and categorical variables. Of the 83 selected cases, expression of Cyclin D1, CD56, CD117 and Ki-67 was identified in 28.9, 34.9, 7.2, and 50.6%, respectively. Cyclin D1 positivity was significantly associated with hypercalcemia. Absence of CD117 expression was noted to be associated with adverse risk parameters including an IgA isotype or light chain disease, International Staging System (ISS) stage III disease, abnormal baseline serum free light chains (sFLC) and a high plasma cell burden. Cyclin D1 expression was congruent with previously reported studies. The frequency of CD56 and CD117 expression was lower than previously reported. This may be due to differences in disease biology between the study populations. Approximately half of cases were Ki-67 positive. Our data showed limited associations between the expression of studied markers and clinicopathologic variables. However, this could be attributed to the small study sample size. We would recommend further characterization of the disease in a larger prospective study with the inclusion of survival outcomes and cytogenetic studies.

Understanding the Constraints and Optimization of Serum Immunofixation Electrophoresis and Serum Free Light Chains for Detecting Monoclonal Proteins: A Single-Center Experience.

Introduction Serum immunofixation electrophoresis (SIFE) and serum free light chain (SFLC) assay are imperative investigations in diagnosis and follow-up of multiple myeloma (MM). SFLC assays are reported to have higher sensitivity than SIFE. However, discrepancies have been reported between them. The current study was aimed at assessing concordance and discordance between SIFE and SFLC results in MM. Methods A total of 450 observations of both SIFE and SFLC were obtained from treatment-naive and follow-up MM patients. Results One hundred and twenty-nine (28.7%) values were observed as discordant, that is, positive SIFE with normal SFLC ratio or negative SIFE with abnormal SFLC ratio ( p -value < 0.00001). Proportion of discordance was higher in SIFE positive-SFLC normal cases than SIFE negative-SFLC abnormal cases. Discordance was more frequent in follow-up cases. Conclusion Negative SFLC alone may not be reliable for MM follow-up. Algorithm may be based on SFLC measurements on each follow-up till attainment of normal SFLC ratio. Once SFLC normalizes, follow-up may be done with SIFE. If SIFE is positive, further follow-up with SIFE may be initiated.

Outcomes in Patients with Renal Monoclonal Immunoglobulin Deposition Disease

BACKGROUND: Monoclonal immunoglobulin deposition disease (MIDD) is characterized by the production of abnormal monoclonal immunoglobulins that deposit in the kidney and other organs. MIDD causes proteinuria, renal damage and eventually renal failure. Currently, there are few studies on the outcomes of patients (pts) with renal MIDD (R-MIDD). METHODS: We performed a single-center retrospective analysis on patients that were seen at the University of California San Francisco Hematology clinic for MIDD from 2010 to 2020. All pts must have had biopsy-proven R-MIDD. Demographic and disease-related characteristics at diagnosis were collected as well therapies administered. Diagnosis of multiple myeloma was per IMWG criteria (Rajkumar et al. Lancet Oncology 2014). Hematologic response and renal response were assessed per previously published criteria (Palladini et al. J Clin Oncol 2012; Palladini et al. Blood 2014). Overall survival (OS), time-to-next treatment (TTNT), time-to-renal progression (TTRP), time-to-dialysis (TTD) were estimated using the Kaplan-Meier method. TTRP was defined as time from the start of treatment to renal progression censored by last follow-up or date of renal transplant. TTD was defined as time from start of treatment to dialysis or last follow-up. Pts already on dialysis at diagnosis were excluded from TTRP and TTD. RESULTS: Thirty-four pts with R-MIDD were identified, 31 light chain deposition disease, 2 heavy chain deposition disease and 1 light and heavy chain deposition disease. Median age at diagnosis was 63 (IQR 58-70) with 13 (38.2%) females. Median creatinine and estimated GFR at diagnosis were 2.80 mg/dL (IQR 3.17-5.57) and 25 ml/min/1.73m2 (IQR 13-40) respectively. Median involved free light chain (FLC) was 819 mg/L (IQR 130-2870), and difference in FLC 433 mg/L (IQR 85-1022). All pts had abnormal serum free light chains and 25 (73.5%) pts had kappa R-MIDD. Median bone marrow plasma cells percentage was 19% (IQR 10-38%). The most common cytogenetic abnormality was del 13 in 6/25 pts (24.0%). A concurrent diagnosis of myeloma was presented in 10 (32.3%) pts. Pts underwent a median of 2 lines of treatment (IQR 1-2). Median follow-up was 5.95 years (range 0.27 - 22.3 years). Pts were treated at induction with the following therapies: Group 1) immunomodulatory drug (IMiD) +/- bortezomib (Bor) (8/34, 23.5%); Group 2) Bor without IMiD (24/34, 70.6%) or Group 3) other (2/34, 5.9%). Autologous stem cell transplant (ASCT) was performed in 82.4% of pts. The 3- and 6-month hematologic response of ≥VGPR was 30.4% (7/23) and 55.6% (15/27) respectively. At the 6-month, Group 1, 2 and 3 had a ≥VGPR of 14.3%, 26.3% and 100% respectively though Group 3 only had 2 pts. Of the 29 pts assessed for best renal response, 9 pts (31.0%) had a renal response. Best renal response for group 1, 2, and 3 occurred in 0%, 38.1% and 100% of pts, respectively. Median TTNT was 2.9 years. Of 34 pts, only 5 died and median overall survival was not reached (Fig.1A). Improved median OS was associated with diagnosis after 2010 v ≤2010 (p=0.1) (Fig. 1B), >60 years old at diagnosis v ≤60 (p=0.1) (Fig. 1C) and treatment with ASCT (p=0.058) (Fig. 1D), though none met statistical significance. Renal progression occurred in 63.3% pts with median TTRP of 1.8 years. Dialysis dependence occurred in 33.3% pts with median TTD not reached (Fig. 2A). TTD did not differ significantly for pts diagnosed >2010 v ≤2010 (p=0.9) (Fig. 2B), ASCT (p=0.7) (Fig. 2D) though was better for pts who were diagnosed >age 60 vs ≤60 (p=0.027) (Fig. 2C). Five pts had a renal allograft, 3 of whom received the allograft after chemotherapy initiation, with 1 graft failure. In a landmark analysis at 6 months, OS and TTRP was better in pts with ≥VGPR compared to <VGPR, though both did not meet statistical significance (p=0.3 and p=0.2, respectively) (data not shown). No significant difference between ≥VGPR compared <VGPR was observed in TTD (p=0.5) (data not shown). CONCLUSION: In this limited retrospective study, we showed that R-MIDD pts were diagnosed late in the disease when pts already developed severe CKD. R-MIDD pts frequently had a concomitant diagnosis of multiple myeloma. Despite treatment with novel agents and ASCT, only a third of pts had a renal response and a third of pts required eventual dialysis. This study highlights the need for early diagnosis of R-MIDD and better treatments for this disease. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

P21 The fly in the ointment: a rare cause of cytopaenia

Introduction/BackgroundThose working in Rheumatology frequently encounter cytopaenia both as adverse effects of many conventional and biological disease modifying drugs and as manifestations of autoimmune diseases. In cases where cytopaenia progresses, other explanations should be sought. Here we present an unusual cause of cytopaenia, seen in a patient with psoriatic arthritis on immunosuppression.Description/MethodAn 81-year-old woman with a diagnosis of psoriatic arthritis had been maintained on Infliximab (3mg/kg 8 weekly) and Methotrexate (7.5mg PO weekly) for 12 years. She then developed mild neutropaenia (1.52 x 109/L). Methotrexate was stopped and she continued on Infliximab monotherapy for several months, until ongoing neutropenia resulted in Infliximab being withheld. Sustained mild neutropenia and the development of thrombocytopenia (platelets 95 x 109/L) prompted a referral to Haematology, who suspected autoimmune neutropenia and advised checking haematinics and monitoring the FBC monthly. The neutropenia improved and Infliximab was restarted.Over 6 months she developed gradually worsening and persistent pancytopenia (neutrophils 1.36 x 109/L, platelets 134 x 109/L, Hb 91 g/L). There was no history of fevers, night sweats, bone pain, headaches, recurrent infections, lumps or bumps, chest symptoms, change in bowel habit or urinary symptoms. Examination revealed no pallor, jaundice, clubbing, peripheral lymphadenopathy or sternal tenderness. The chest was clear and the abdomen soft with no organomegaly.Repeat bloods showed microcytic hypochromic anaemia (Hb 86 g/L, MCV 73 fL, MCH 24.6 pg) with target cells on blood film. Iron was low (iron 5.1 umol/L, transferrin 1.52 g/L). Serum protein electrophoresis showed paraprotein bands with abnormal serum free light chain assay possibly consistent with myeloma, lymphoma or MGUS. Haematology suspected myelodysplasia, potentially secondary to previous long term Methotrexate therapy. A bone marrow biopsy was performed; the unexpected result was Leishmaniasis. Our patient was admitted to hospital and, following microbiology review, was treated with liposomal amphotericin (IV) for Visceral Leishmaniasis as an inpatient. Her Infliximab was suspended and her joints have remained quiescent.Discussion/ResultsLeishmania is an intracellular parasitic protozoan that is transmitted to humans by sandfly bites. It is endemic in Africa, America, Central Asia and the Mediterranean. It usually has an incubation period of 3-8 months. Those who are immunosuppressed, for example due to immunotherapy or HIV, are at increased risk of infection. The patient had only ever travelled to Portugal and Gibraltar. One trip to Gibraltar occurred whilst on dual immunosuppression with Infliximab and Methotrexate and prior to the development of neutropenia. She has no recollection of any insect bites.Visceral leishmaniasis is variable in the severity of symptoms experienced ranging from asymptomatic to a febrile illness with lymphadenopathy, hepatospenomegaly, night sweats, cutaneous pigmentation, appetite loss and weight loss, which can be drastic. Our patient indeed described significant weight loss in the preceding year.This case demonstrated the laboratory abnormalities which are typical of Visceral Leishmaniasis: pancytopenia and hypergammaglobulinaemia.Treatment for visceral Leishmaniasis has classically been with pentavalent antimonials (based on the heavy metal antimony) such as Sodium stibogluconate. Their toxicity profile and growing resistance however has meant amphotericin B is often used first line. This is given intravenously, with the liposomal form preferred as it has lower toxicity. Our patient received 4 mg per kg daily on days 1–5, 10, 17, 24, 31, and 38, following the FDA-approved regimen for immunosuppressed patients.Without treatment Leishmaniasis is usually fatal, with haemmorrhage, infection, cachexia and multiorgan failure as causes of death.Key learning points/ConclusionWhilst patients with Rheumatological conditions may have cytopaenia due to their disease or its treatment, persistent, progressive or unexplained results should be investigated further. In patients with cytopaenia of unclear aetiology, thorough investigation with Haematology involvement is mandatory. You may find an unexpected diagnosis … we did!

Monoclonal Gammopathy of Renal Significance: Histomorphological Spectrum at a Tertiary Care Center

Introduction: The term monoclonal gammopathy of renal significance (MGRS) has been described to include patients with renal manifestations associated with circulating monoclonal proteins with or without a clonal lymphoproliferation (B-cell or plasma cell) and not meeting diagnostic criteria for an overt hematological malignancy. A host of MGRS-associated lesions have been described that involve various renal compartments. Our study describes the histomorphological spectrum of MGRS cases at our center in the last 5 years and description as per the classification system of the International Kidney and Monoclonal Gammopathy Research Group (IKMG). Material and Methods: Retrospective analysis was carried out of all the renal biopsies with characteristic monoclonal immunoglobulin lesions for histopathological diagnosis between years 2015 and 2020 and reviewed by two independent pathologists. Results: Most patients in the study belonged to the fifth decade, with a median age of 50 years (mean 50.14 ± 10.43) range (24–68 years) with a male preponderance. Most patients presented with proteinuria as the sole manifestation (66.6%). Many of the patients (48%) had an M spike by serum protein electrophoresis or urinary protein electrophoresis with an abnormal serum free light chain assay (60.8%). AL amyloidosis was the most common diagnosis observed on histopathological evaluation (68.7%), followed by light chain deposition disease (10.4%). Conclusion: MGRS lesions are infrequently encountered in the practice of nephropathology and pose a diagnostic challenge due to the limitation of a congruent clinical or hematological picture. A thorough histological examination with immunofluorescence and electron microscopy often precipitates in the right diagnosis and prompts timely management.

Kidney Histopathologic Spectrum and Clinical Indicators Associated with MGRS.

Patients with monoclonal gammopathy and concomitant kidney diseases are frequently found in clinical practice. Some of them are diagnosed with monoclonal gammopathy of renal significance (MGRS) due to the presence of monoclonal Ig-related kidney injuries. This study aimed to investigate the histopathologic spectrum and clinical characteristics associated with MGRS in a large cohort of patients with monoclonal gammopathy and biopsy-proven kidney diseases from a single Chinese nephrology referral center. Patients who presented with monoclonal gammopathy (monoclonal spike on serum and/or urine immunofixation tests) and underwent kidney biopsy in the Peking University First Hospital from January 1, 1999 to December 31, 2020 were enrolled in this retrospective study. Patients with malignant hematologic diseases were excluded. Clinical and laboratory data were collected from the electronic medical record system. Comparisons of patients with and without MGRS and with and without amyloidosis were performed. The clinical characteristics associated with MGRS were identified using multivariable logistic regression. A total of 700 patients with monoclonal gammopathy and kidney biopsy were identified. Thirteen patients with repeat kidney biopsies were analyzed separately. For the remaining 687 patients with one kidney biopsy, 261 patients (38%) had MGRS lesions, and the rest (426 patients, 62%) had non-MGRS kidney diseases. Ig-related amyloidosis accounted for the most MGRS cases (n=164, 63%), followed by monoclonal Ig deposition disease (n=23, 9%) and thrombotic microangiopathy (n=22, 8%). In the non-MGRS group, membranous nephropathy was the most common diagnosis (n=171, 40%). In the multivariable logistic regression model, the presence of abnormal serum free light chain ratio, older age, and greater proteinuria were independently associated with MGRS. Monoclonal Ig amyloidosis is the leading cause of MGRS in Chinese patients with monoclonal gammopathy. The presence of abnormal free light chain ratio, older age, and greater proteinuria were associated with MGRS.

A Phase II Study of Daratumumab in Patients with High-Risk MGUS and Low-Risk Smoldering Multiple Myeloma

A Phase II Study of Daratumumab in Patients with High-Risk MGUS and Low-Risk Smoldering Multiple Myeloma

Surveillance Functional Imaging Has Limited Role in Solitary Plasmacytomas: International Multi-Centre Study of Clinical Outcomes

BackgroundRisk of recurrence of Solitary plasmacytoma (SP) or progression to Myeloma (MM)/ multiple plasmacytomas (MP) is well established. Standard risk factors (RF) for disease recurrence/ progression include: patient age, SP size, axial location, bone marrow (BM) plasma cell %, and abnormal serum free light chain (SFLC) ratio at diagnosis and M protein persistence post radiotherapy (RT). Data is limited on whether functional imaging parameters can serve as a biomarker for risk of recurrence/progression.Methods:We conducted a retrospective analysis of 66 SP patients (23 UK, 43 Brazil) over a 15 yr period. We recorded patient and disease characteristics at baseline including SFLC, BM examination, imaging by skeletal survey, CT/MRI and functional imaging by 18F-FDG PET CT or 99mTc-Sestamibi MIBI(SPECT/CT or planar). Follow-up (FU) functional imaging was performed as routine surveillance or suspicion of disease recurrence/progression. The proportion of patients progressing to MP/ MM was recorded. Disease recurrence/progression was defined as the detection of new SP/ MP on FU functional imaging or biochemical relapse. Effect of surgery and RT on disease recurrence/progression was analysed. PFS and OS from diagnosis and time of repeat functional imaging were measured using Kaplan-Meier estimates. Factors examined for their predictive value of progression risk included: initial SP size, location, surgical resection, RT dose, baseline SFLC, functional imaging findings and clinical context of repeat scanning. Log-rank test was used for univariate testing and multivariate Cox analysis.ResultsMedian patient age was 60 yrs (19-82 years). SP location was bone (83%) and extramedullary (EMP) (19.7%). Median SP size was 60mm (range 19-220mm). BM results were available for 56/66 patients, median PC % 0.1% (range 0-9.2%, IQR 0-2.9%).Median FU 53.6M (range 5.8-327 months) with 9 deaths (6/9 disease progression related). On FU 31/66 patients (47.0%) never progressed. One patient (7.7%) had recurrent SP in EM location, 6 (11.3%) as bony SP and 28 (42.4%) progressed to MM/MP. The cumulative incidence of progression to MP/ MM was 49.9% at 5 years (95% CI 35.6-62.6%), bone SP 57.7% (95% CI 21.7-48.6%) EMP 19.8% (95% CI 2.4-49.4%) (fig. 1).OS was 90.7% (95%CI 79-96%) 5 yrs from diagnosis, median PFS was 61M with no significant difference in PFS or OS between centres. RFs for progression to MM included bone SP compared to EMP (log rank p=0.0265)(fig. 2). Size of SP had no effect on outcome. Baseline SFLC correlated positively with lesion size but was not predictive of outcome.57/66 (86.4%) received RT, either radical (≥40Gy N=46, 80.7%) or “palliative” dose (<40Gy, N=11, 19.3%). Patients treated with less than 40 Gy showed more PFS events, (chi-square 4.61, p=0.032)(fig. 3). Surgical resection had no effect on PFS (p=0.5). 6 patients received systemic chemotherapy at presentation, 5/6 remain in remission after a median follow-up of 10yrs.All patients in the UK cohort had PET-CT (n=23), the Brazilian cohort was imaged by MIBI (n=11). FU imaging was performed in 62.1% cases at a median of 174 days ~ 6 months post diagnosis. 16 patients (39%) were scanned on suspicion of relapse, 9/16 (56.2%) showed progressive disease. 20 patients (48.7%) were scanned as routine surveillance, one patient (5%) showed disease progression. FU PET SUVmax was not useful in predicting outcome.The positive predictive value of FU imaging to determine clinical outcome was high (100%) regardless of if the scan was for surveillance/suspected progression. Negative predictive value was low (60%, 95%CI: 40.6%-77.3%) and particularly poor (14.3%, 95%CI: 0.4-58%) in suspected relapse, suggesting more diffuse infiltration in BM.ConclusionThis large retrospective dataset of SP patients from UK and Brazil shows no difference in PFS and OS despite variability in racial distribution and access to treatment. We have confirmed bony location and use of <40GY as RFs for disease progression. SFLC ratio and size of SP were not RFs for progression. Based on our results use of upfront adjuvant chemotherapy is worth prospective evaluation (IDRIS trial in UK). Our data suggests functional imaging should be used when there is suspicion of relapse/progression and not as a routine surveillance tool. Observations from our large real world plasmacytoma cohort regarding value of functional imaging are hypothesis generating, but need confirmation prospectively. [Display omitted] DisclosuresRamasamy:Celgene: Honoraria, Other: Research Grant; Janssen: Honoraria, Other: Research Grant.

Anaplastic Myeloma Arising from Myeloma: Successful Management of Two Diseases in an Individual

IntroductionMultiple myeloma is known to have progressive mutations that lead to a dominant aberrant plasma cell clone and a number of subclones. Mutations can lead to more aggressive forms of myeloma, but rarely does it transform into an immature variant such as anaplastic myeloma. This particular variant has a predisposition for extramedullary sites and is related to IgA plasma cell variants. Unlike standard myeloma that responds better to novel agents such as proteasome inhibitors and immunomodulators, this poorly differentiated cell is highly resistant to therapy and has very poor outcomes.In the following case report, we present a patient with IgA kappa anaplastic myeloma that evolved from multiple myeloma. We will demonstrate how a combination of novel agents in conjunction with conventional chemotherapy was a successful therapy for both plasma cell variants.Case ReportA 60 year-old man had a three month history of confusion, headaches, and leg weakness. He did not seek medical attention until he lost vision on his right eye. On exam, he had right ptosis with a dilated pupil fixed downward and laterally. MRI of the orbit showed a right orbital apex mass surrounding the optic nerve and diffuse leptomeningeal enhancement. A PET/CT, to better characterize the extent of disease showed right laryngeal, lung, and femoral hypermetabolic lesions in addition to the orbital mass. A biopsy of the laryngeal mass showed an IgG kappa anaplastic myeloma with Ki-67 of 70% and FISH positive for +12 and +14. Serology demonstrated an IgA M-spike of 1.56 with an abnormal serum free light chain ratio of 118.31. He underwent a bone marrow biopsy that showed 30% kappa-restricted plasma cells with 13q- and +11 by FISH and a lumbar puncture that demonstrated CNS involvement by CD38+ clonal plasma cells. He was classified as systemic stage I IgA kappa myeloma by R-ISS with localized anaplastic myeloma showing similar light chain restriction by immunohistochemistry.The patient received HD methotrexate 3 g IV with evidence of leptomeningeal response but evidence of sytemic progression on eye mass within a week despite of stable myeloma serology. He received 4 Gy as a single dose to the eye mas that shrunk the tumor. HyperCVAD with IT cytarabine alternating with MTX was started with a significant improvement in plasmacytomas by PET scan after 2 cycles of therapy. Flow cytometry from CNS became negative at that time but paraprotein remained unchanged.A bone marrow biopsy performed after the 4th cycle of chemotherapy showed 30% clonal plasma cells with stable M-spike at 1.45 and serum free light chain ratio of 79. Seeing that the CNS fluid was now negative and the orbital and leptomeningeal lesions had improved, therapy was changed to carfilzomib, pomalidomide, and dexamethasone but continued on IT chemotherapy alternating cytarabine and MTX. His M-spike resolved after 3 cycles of treatment. His immunofixation continued to detect IgA kappa clone and serum free light chain ratio dropped to 19.08.Follow upThe patient continues tolerating treatment with no evidence of systemic or CNS relapse disease. He remains on carfilzomib, pomalidomide, and dexamethasone as maintenance for systemic therapy combined with monthly IT chemotherapy. He developed one episode of confusion thought to be from white matter changes from IT chemotherapy but those symptoms have resolved.DiscussionThis unique scenario of a patient having both myeloma and anaplastic myeloma poses a challenge in management. While novel agents may be good to control the myeloma, more primitive forms of myeloma cells do not have the epitopes these agents bind to in order to cause cell destruction. Since anaplastic myeloma is more aggressive, targeting it with conventional chemotherapy that penetrated the CNS barrier seemed like a good initial treatment until CNS disease control was achieved, with focus on the more indolent myeloma afterwards with novel agents. Out of those, we included one known to have CNS penetration (pomalidomide). This approach was effective in this case and could be applied in future cases as clinical trials on such rare disease wouldn't be feasible.The similarities between the two plasma cell neoplasms shows the significant difference myeloma subclones can have. This proves the concept that myeloma does not behave as a single tumor, but more like clusters of different myeloma strains that can branch off the dominant clone and lead to relapse or refractory disease. DisclosuresRodriguez:Celgene: Other: advisory board, Speakers Bureau; Takeda: Speakers Bureau.

MO297MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE: A REPORT OF CASES FROM FOUR PORTUGUESE CENTERS

Abstract Background and Aims Monoclonal gammopathy of renal significance (MGRS) refers to any plasma cell or B cell clonal lymphoproliferation that has at least one kidney lesion related to the monoclonal immunoglobulin productions plus, the underlying clone is not responsible for tumour complications. Plus, does not meet any haematological criteria for specific treatment. Although considered a non-malignant or smouldering hematologic condition, its effects on the kidney are not benign since it frequently evolves to end-stage renal disease. There has been some reluctance in treating these patients but increasing evidence has shown that renal outcomes are closely associated with the haematological response to chemotherapy. We aimed to evaluate the incidence of MGRS in the North of Portugal and to assess patients’ characteristics, treatment and follow-up. Method We have, retrospectively, collected information of all patients with a biopsy proven MGRS diagnosis, from four Portuguese centers. Demographic, clinical, laboratorial data and treatment were analysed. Follow-up was made until dialysis start, death of until December 2020. Survival curves were analysed according to the treatment performed, the histological diagnosis, the type of chains, the estimated glomerular filtration rate (eGFR) and proteinuria at the time of diagnosis. Baseline characteristics were reported as mean ± standard deviation (SD) and median (min-max) for continuous variables or as number (percentage) for categorical variables. Survival curves were analysed using Kaplan–Meier method. Statistical calculations were performed using SPSS. Results Our study included 36 patients, with a mean age of 69 ± 11 years old and 52,8% were males. At baseline, the median value of serum creatinine (sCr) was 1,2 (0,4-6,3) mg/dL, which represented a mean eGFR of 55,4 ± 30,4 ml/min/1,73 m2 according to the CKD-EPI formula. The nephrotic syndrome was the most common (72%) renal presentation. The median proteinuria value was 8,0 (0,5-28) g per day and the mean albumin value was 2,7 ± 0,8 g/dL. The mean value of monoclonal protein was 5,5 ± 4,8 g/L with 62,5% of the patients having an abnormal serum free light chain ratio. Table 1 describes the type of gammopathy found, being the IgG/Kappa the most observed. The immunoglobulin light chain amyloidosis (AL amyloidosis) and the monoclonal immunoglobulin deposition disease (MIDD), mainly light chain deposition disease (LCDD) were the most frequent histological diagnosis (Table 2). Monoclonal gammopathy of undetermined significance (MGUS) was the most frequent haematological diagnosis (Table 3). Treatment was done in 75% of the cases and bortemozib-based regimens were the most used. Three patients (8,3%) received a bone marrow auto transplant. Approximately 40% of the patients had complete haematological and renal response. Treatment regimens and haematological and renal responses are summarized in Table 4 and 5. Survival curves (Figures 1–2) were significantly higher in younger patients (p=0,039) and both renal and global survival were better (p=0,023) in MIDD compared to AL amyloidosis. No statistically significant differences were detected when analysing according to treatment, type of chain, eGFR, proteinuria and serum albumin at admission. Conclusion The incidence of MGRS is probably underestimated and its treatment is yet far to be universal. In our series, 25% of the patients weren’t proposed to any treatment. MGRS approach requires a multidisciplinary team composed by Nephrologists, Pathologists, Onco-Haematologists and a Bone Marrow Transplantation department. Since not all hospitals meet these conditions, referral centers of greater expertise are required for a prompt diagnosis and to provide the most adequate treatment. We hope that in a near future more centres join this project and that this represents the first step towards the creation of a Portuguese group dedicated to the study and treatment of MGRS.

Neuropathy associated with IgA monoclonal Gammopathy. A harbinger of AL amyloidosis

Peripheral neuropathy is seen in 15% of patients with IgA monoclonal gammopathy. Treatment and prognosis of dysproteinemic neuropathy is usually guided by the underlying plasma cell disorders, which could be either benign or malignant. The true incidence of hematologic malignancy in patients with neuropathy associated with IgA monoclonal gammopathy is not known. However, patients with IgA M-protein are generally at increased risk for malignant transformation. Since neuropathy may be the first and only organ involvement, neurologists are key contributors in identifying each patient's plasma cell dyscrasia. We report two patients who presented with severe progressive polyneuropathy, had a detectable low-level IgA lambda paraproteinemia dismissed as incidental. Both were diagnosed later with a combination of malignant plasma cell dyscrasia and AL amyloidosis resulting in multiorgan failure and death. Both patients demonstrated red flags for malignant progression including abnormal serum free light chain, rapidly progressive debilitating neuropathy refractory to immunotherapy, prominent autonomic dysfunction, and weight loss. In summary, patients with IgA monoclonal gammopathy presenting with polyneuropathy can be at risk for malignant transformation. Failure to investigate for hematologic malignancy and AL amyloidosis may cause significant delays in treatment and result in fatal outcomes.

Phase 2 Trial of Ixazomib, Cyclophosphamide and Dexamethasone for Treatment of Previously Untreated Light Chain Amyloidosis

Phase 2 Trial of Ixazomib, Cyclophosphamide and Dexamethasone for Treatment of Previously Untreated Light Chain Amyloidosis

Body Mass Index and Clinical Factors Associated with Monoclonal Gammopathy of Undetermined Significance (MGUS) Progression in Olmsted County, Minnesota

Introduction Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant clonal disorder, which progresses at a rate of 1% per year to multiple myeloma (MM), or other plasma-cell or lymphoid disorders. MGUS is common and occurs in approximately 3% and 5% of persons 50 and 70 years of age or older, respectively. Clinical factors reported to be associated with MGUS progression include MGUS isotype, abnormal serum free light-chain ratio (FLCr), and high serum monoclonal protein (M protein) level (&amp;gt;=1.5 g per deciliter). Body mass index (BMI) has also been seen associated with MGUS progression, but has not been evaluated in context of established clinical prognostic factors. Here, we evaluate the contribution of BMI to MGUS progression beyond clinical prognostic factors in a population-based study and examine differential associations by sex. Methods We studied 594 patients residing in Olmsted County Minnesota, who were identified with MGUS in a screening study conducted between1995 through 2003. Patients with light-chain MGUS were not included. Patients were screened for M-protein [normal (&amp;lt;1.5 g/dl) or high (≥1.5 g/dl)], FLCr [normal (0.26-1.65) or abnormal (&amp;lt;0.26 and/or &amp;gt;1.65)], and isotype (IgG, IgM, IgA, bi-clonal). Follow-up time was calculated from date of MGUS screening to date of last follow-up, death, or progression to MM or another plasma-cell or lymphoid disorder. BMI (kg/m2) was calculated using height and weight values reported close to sample date (80% of patients within 2 years), and then categorized into BMI&amp;lt;25 and BMI≥25. We used Cox regression to estimate the association of BMI with risk of MGUS progression to MM or another plasma-cell or lymphoid disorder, univariately, and accounting for clinical factors. Analyses were also stratified by sex. We report hazard ratios (HR) and 95% confidence intervals (CI). Results Of the 594 patients, 51% were male, and the median age at screening date was 73 (range:50-98 years). The immunoglobulin type was IgG in 71% of patients, IgM in 17%, IgA in 10%, and bi-clonal in 2%. High M protein level was observed in 22% and abnormal FLCr in 28%. BMI≥25 was observed in 67% of patients. The median follow-up time was 10.5 years (range:0-25). Over a median of 6,846 person-years, 465 patients (78%) died and 57 patients progressed and developed MM (N=39), amyloidosis (N=8), lymphoma (N=5), or Waldenstrom macroglobulinemia (N=5). The overall rate of progression was 0.87 events (CI:0.67-1.12) per 100 person-years, and higher among males (1.01, CI:0.73-1.42) than in females (0.72, CI:0.48-1.08), however, the difference was not statistically significant (P=0.24). In univariate analyses, BMI≥25 (HR=2.14, CI:1.05-4.36, P=0.04), non-IgG isotype (HR=2.84, CI:1.68-4.80, P=0.0001), high M protein (HR=2.57, CI: 1.50-4.42, P=0.001), and abnormal FLCr (HR=3.39, CI:1.98-5.82, P&amp;lt;0.0001) were associated with increased risk of progression (Table 1.A). These four factors were independently associated with MGUS progression in a multivariable model, with a c-statistic=0.75 (CI:0.68-0.82). When stratifying by sex, associations of BMI with progression were stronger among females than males (Table 1.B) [c-statistic=0.81 (CI:0.72-0.90) vs 0.71 (CI:0.60-0.82) for females vs. males respectively], however, a test for interaction between BMI and sex was not statistically significant (P=0.15). Conclusions In this study we found evidence that high BMI is a prognostic factor independent of isotype, M protein, and FLC ratio in the full cohort, however, this was mainly driven by the effect in females rather than males. Future studies should further investigate sex differences in evaluating prognostic factors among MGUS patients. Disclosures Dispenzieri: Intellia: Research Funding; Pfizer: Research Funding; Alnylam: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Janssen: Research Funding. Kumar:Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Cellectar: Other; Kite Pharma: Consultancy, Research Funding; Tenebio: Other, Research Funding; BMS: Consultancy, Research Funding; Karyopharm: Consultancy; MedImmune: Research Funding; Sanofi: Research Funding; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Merck: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Genecentrix: Consultancy; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Dr. Reddy's Laboratories: Honoraria; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Novartis: Research Funding; Carsgen: Other, Research Funding; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member.

P0204PREVALENCE AND PREDICTIVE FACTORS OF BIOPSY-PROVEN NEPHROPATHY RELATED TO MONOCLONAL GAMMOPATHY

Abstract Background and Aims The prevalence of monoclonal gammopathy (MG) and kidney disease increases with age. When a patient present with both conditions, it is often necessary to perform a kidney biopsy in order to rule out a Monoclonal Immunoglobulin-Related Nephropathy (MIRN) that may require a specific therapy that targets either an overt hematological malignancy or a MG or Renal Significance (MGRS). The aim of our study was to identify factors that predict the presence of MIRN in this setting. Method This retrospective monocentric study included all patients who underwent a kidney biopsy between 2007 and 2018 with concurrent presence of GM, as defined by positive serum immuno-electrophoresis and/or Bence-Jones proteinuria. Results 328 patients were included, representing 11.8% of all kidney biopsies performed in our center during this period. Indication of biopsy was renal failure (eGFR &amp;lt;60ml/min/1.73m) in 77.4% of cases and/or proteinuria (urine protein-to-creatinine ratio &amp;gt;0.5g/g) in 75.9% of them. Median (IQR) serum creatinine was 155 μmol/L (111-233), eGFR 37.5 (22-56) ml/min/1.73m, serum albumin 29.5 (24-35) g/l. Median age was 67 (57/75), the M/F ratio was 198/130, diabetes mellitus was present in 21.3% of cases, hypertension in 53.1%. Kidney biopsy revealed that nephropathy was related to MG in 91/328 patients (27.7%). Myeloma cast nephropathy and AL amyloidosis were the most common histopathological subtypes (36 and 34% respectively), followed by monoclonal immunoglobulin deposition disease (15%) and cryoglobulinemic glomerulonephritis (8%). Patients with MIRN had more severe renal function impairment with median (IQR) serum creatinine of 176 (119-307) vs 149 (108-216) μmol/l (p=0.003) and heavier proteinuria, 3.9 (2.2-8.2) vs 2.0 (0.9-5.2) g/g (p&amp;lt; 0.001), when compared to non-MIRN patients. Hematological malignancy was diagnosed in 83 cases (25,3%) (Multiple Myeloma in 62, non-Hodgkin Lymphoma in 6, Waldenström Macroglobulinemia in 6, Chronic Lymphoid Leukemia in 6, Plasmocytoma in 3). Among them, MIRN was diagnosed in 51 (61%) cases but tumoral lympho-plasmocytic infiltration was observed in 9 (11%) cases. In this subgroup of patients, no laboratory test could predict the presence of a specific nephropathy. Among patients with no hematological malignancy (n=245), MIRN was diagnosed in 40 cases (16%) to confirm MGRS diagnosis. The markers that were most commonly associated with the presence of MGRS were positive Bence-Jones proteinuria (OR 4.7; 95%CI 2.2-10.3; p&amp;lt; 0.001), abnormal serum Free Light Chain (FLC) ratio (OR 4.2; 95%CI 1.7-10.7; p&amp;lt; 0.001), and serum electrophoresis spike &amp;gt;1.5 g/l (OR 5.9; 95%CI 2.6-13.5; p&amp;lt; 0.001). However, none of those markers had sufficient power to formally predict the result of the biopsy, as positive (PPV) or negative (NPV) predictive values were 36/41/45 % and 89/86/88 % respectively. Conclusion Almost one-third of patients with MG and kidney disease referred to our Department have biopsy-proven related nephropathy. Although negativity of Bence-Jones proteinuria and a normal serum FLC ratio are frequently associated with the absence of MGRS, kidney biopsy, beyond its diagnostic and prognostic interest, remains the most discriminating test.

P0480LENALIDOMIDE PLUS DEXAMETHASONE FOR PROLIFERATIVE GLOMERULONEPHRITIS WITH MONOCLONAL IG DEPOSITS

Abstract Background and Aims To evaluate the efficacy and safety of lenalidomide plus dexamethasone (LD) in patients with proliferative glomerulonephritis with monoclonal Ig deposits (PGNMID). Method Retrospectively analyzed the clinicopathological data of 6 PGNMID patients who treated with LD protocol from January 2010 to October 2019. Results All of the patients received LD treatment for ≥3 months after renal biopsy. 3 patients achieved renal remission. The renal remission rate was 50%. Light microscopy showed membranoproliferative glomerulonephritis and immunofluorescence showed single kappa type IgG3 was deposited in the mesangial region and the vascular loop. Before taking LD scheme, the median urinary protein were 7.76 (1.27,14.57) g/24h, the median serum creatinine 1.34 (0.8,3.27) mg/dL, the median albumin 34.5 (22.4,37.5) g/L. In 5 patients the concentration of serum free kappa and lambda light chain increased, but no patients with abnormal serum free light chain ratio. Complement C3 deteriorated in 2 patients, 2 cases of patients with monoclonal plasma cells, 0.7% and 0.5%, respectively. Immunofixation electrophoresis suggested that 1 patient had positive serum M protein for kappa type IgG3. At the last follow-up, median urine protein was 3.33 (0.33,11.23) g/24h, median serum creatinine was 1.23 (0.91,1.82) mg/dL, and median albumin was 35.9 (24.5,45.6) g/L. The concentration of 4 patients with elevated serum free light chain was lower than that before taking the drug. Two patients with decreased complement C3 increased to normal concentration at the last follow-up. However, the other two patients had a slight decrease in complement C3. The M spike did not turn negative during the follow-up in one patients. Adverse events included anemia, neutropenia, limb numbness, upper respiratory tract infection. Conclusion This study reported that lenalidomide plus dexamethasone may be effective in treating proliferative glomerulonephritis with monoclonal Ig deposits for the first time. More attention needs to be paid to the hematological adverse events during lenalidomide treatment.