Improving Outcomes in Patients with Renal Failure Secondary to Multiple Myeloma: Results From ChAR2M2.

Abstract Abstract 1875 Poster Board I-900 Study purpose: To explore how free light chain (FLC) removal by high cut-off haemodialysis (HCO-HD) has been adopted into clinical practice for the management of renal failure secondary to multiple myeloma. Describing treatment patterns and the laboratory and clinical outcomes associated with its use. Methods: A chart audit of patients treated with FLC removal by HCO-HD, using the Gambro HCO 1100 dialyser, was performed in 16 dialysis centers across 9 countries. Patient demographics, treatment patterns and dialysis side-effects were recorded. In addition, the following outcomes were measured: dialysis independence and reductions in serum FLCs concentrations at 12 and 21 days. Results: Data for 66 patients was entered. Patients had an average age of 65.1 (SD×10.1); 42 of them (63.64%) were male and 24 (36.36%) were female. Sixteen (24%) presented with relapsing myeloma and 50 (76%) had de novo disease. On average, each patient received 13 HCO-HD sessions (SD×8). Forty-one patients became dialysis independent (62.12%), after an average of 12 sessions. Dialysis related side-effects were reported in 6% of all patients. Forty patients (60.61%) were reported to have a sustained reduction in serum FLC concentrations by day 12. By day 21 this had increased to forty-one (62.12%). Among the patients who achieved a sustained reduction in serum FLC concentrations, 28 (70%) had a decline in FLC levels of more than 50% by day 12 and 34 (82.93%) by day 21. Among patients who achieved sustained reduction of more than 50% in serum FLC concentrations by day 12, 75% became dialysis independent. In comparison only 53% of those with a reduction of less than 50% became dialysis independent (p×0.007). Furthermore, among patients who achieved sustained FLC reduction of greater than 75%, 81% became dialysis independent. The rate of dialysis independence was also significantly higher in patients with de novo disease compared with those with relapsing myeloma (64% versus 56%, p×0.04). Conclusion: Free light chain removal by HCO-HD was well tolerated and associated with a very high rate of dialysis independence in patients with renal failure secondary to multiple myeloma. Rates of renal recovery were greater in patients with de novo myeloma and those who achieved an early reduction in serum FLC concentrations. Disclosures: No relevant conflicts of interest to declare.

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Bortezomib with Dexamethasone in Newly Diagnosed Patients with Primary Systemic Light Chain Amyloidosis or Multiple Myeloma-Associated AL Amyloidosis

Blood ◽

10.1182/blood.v120.21.5036.5036 ◽

2012 ◽

Vol 120 (21) ◽

pp. 5036-5036 ◽

Cited By ~ 1

Author(s):

Beihui Huang ◽

Juan Li ◽

Junru Liu ◽

Dong Zheng ◽

Mei Chen ◽

...

Keyword(s):

Multiple Myeloma ◽

Side Effects ◽

Light Chain ◽

Conflicts Of Interest ◽

Complete Response ◽

Al Amyloidosis ◽

Newly Diagnosed ◽

Hematologic Response ◽

Best Response ◽

Organ Response

Abstract Abstract 5036 Objective: To assess the efficacy and tolerability of bortezomib with dexamethasone for patients with primary systemic light chain (AL) amyloidosis or multiple myeloma-associated AL amyloidosis. Methods: Twelve newly diagnosed patients with primary systemic AL amyloidosis and six patient with multiple myeloma-associated AL amyloidosis were treated with a combination of bortezomib (1. 3 mg/m2 d1, 4, 8, 11) and dexamethasone (20 mg d1–4). Results: Sixteen patients was evaluable. 12/16 had a hematologic response and 6/16 (37. 5%) a hematologic complete response. Median cycles to response was 1 cycle and median cycles to best response was 2 cycles. In patients with primary AL amyloidosis, 8/10 (80. 0%) had a hematologic response and 5/10 (50. 0%) a hematologic complete response. In patients with myeloma-associated AL amyloidosis, 7/10 (70. 0%) had a hematologic response and 1/6 (16. 7%) a hematologic complete response. Twelve patients (75. 0%) had a response in at least one affected organ, in which 7 in patients with primary AL amyloidosis and 5 in myeloma-associated AL amyloidosis. Person correlation between hematologic response and organ response was 0. 667 (p=0. 005). Fatigue, diarrhea and infection were the most frequent side effects. Three patients developed herpes zoster and had to stop chemotherapy. Conclusions: VD produces rapid and high hematological responses in the majority of patients with newly diagnosed AL regardless of primary or associated with myeloma. It is well tolerated with few side effects. This treatment may be a valid option as first-line treatment for newly diagnosed patients with primary systemic AL amyloidosis and multiple myeloma-associated AL amyloidosis. Disclosures: No relevant conflicts of interest to declare.

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Combined Chemotherapy and High Cut-Off Hemodialysis Improve Outcomes in Multiple Myeloma Patients with Severe Renal Failure.

Blood ◽

10.1182/blood.v110.11.3610.3610 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3610-3610 ◽

Cited By ~ 2

Author(s):

Colin A. Hutchison ◽

Mark Cook ◽

Supratik Basu ◽

Paul Cockwell ◽

Kolitha Basnayake ◽

...

Keyword(s):

Multiple Myeloma ◽

Renal Failure ◽

De Novo ◽

Renal Recovery ◽

Severe Renal Failure ◽

Cast Nephropathy ◽

Kaplan Meier ◽

Sustained Reduction ◽

Rate Of Recovery ◽

And Control

Abstract Irreversible acute renal failure (ARF) is associated with significantly increased morbidity and mortality in multiple myeloma (MM) patients. 10% of MM patients require dialysis support and of these 80% remain dialysis dependent. Cast nephropathy from excess serum free light chains (sFLC) accounts for approximately 70% of dialysis-dependent ARF in this setting. We recently reported preliminary studies demonstrating high cut-off hemodialysis (HCO-HD) as a novel method for FLC removal in MM patients (JASN, March, 2007). The purpose of this subsequent study was to two fold: Firstly, to determine the safety and effectiveness of HCO-HD to result in sustained reductions in sFLC concentrations in cast nephropathy patients. Secondly, to compare renal recovery rates in patients treated with FLC removal HD with a case-matched historical control population. Methods: 25 patients with dialysis dependent ARF and MM were assessed for inclusion. 3 patients were not suitable for renal biopsy. Renal biopsies demonstrated cast nephropathy in 20 of 22 patients. Only 18 patients commenced treatment as 2 were not suitable for chemotherapy. Thalidomide/dexamethasone regimes were used for patients with de novo MM and bortezomib/doxorubicin/dexamethasone for relapsing patients. FLC removal HD was undertaken using the Gambro HCO 1100™, for extended periods of 8 hours/day. Extended dialysis was supported by replacement of albumin, magnesium and calcium by protocol. Historical age matched control patients received standard high flux dialysis (n=18). Results: There were no complications related to FLC removal HD. However, 6 of the 18 patients developed infections requiring intervention. The percentage reductions, in sFLC concentrations, achieved by days 5, 12 and 21 were 54 (0–71), 66 (0–88) and 57 (0–88), respectively. There were no significant differences in presenting serum creatinine, sFLC type or concentration between the treatment and control groups. 13 of 18 patients (72%) in the treatment group became independent of dialysis versus 2 of 18 controls (11%, P<0.0001(Figure)). This historical rate of recovery is consistent with the published range of 2–20%. The 13 patients who became independent of dialysis following FLC removal HD achieved a median sustained reduction in sFLC concentrations of 86% (50–93). Their median time to independence of dialysis was 24 days (13–50) with an estimated GFR three months following commencement of treatment of 44mls/min/1.73m2 (29–60). The 5 patients who did not achieve independence had not attained sustained reductions in sFLC concentrations. 4 of these had chemotherapy withheld because of infections, the other had progressive disease not responsive to bortezomib based chemotherapy. Renal recovery was associated with improved Kaplan-Meier survival, P<0.02. Conclusion: Extended HCO-HD and effective chemotherapy resulted in rapid and sustained reductions in sFLC concentrations with no adverse events. Together, these interventions increased the rate of renal recovery in multiple myeloma patients with cast nephropathy. Figure Figure

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No Recurrent Mutation of SF3B1, U2AF1 and SRSF2 Spliceosomal Gene in Multiple Myeloma but Polymorphisms of These Genes Are Associated with the Prediction of Worse Prognosis

Blood ◽

10.1182/blood.v120.21.3958.3958 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3958-3958

Author(s):

Trang Nguyen Thi Dai ◽

Hye-Ran Kim ◽

Min-Gu Kang ◽

Stephanie J. Won ◽

Hwan-Young Kim ◽

...

Keyword(s):

Multiple Myeloma ◽

Light Chain ◽

Somatic Mutations ◽

Conflicts Of Interest ◽

Bone Lesion ◽

Disease Free Survival ◽

Free Light Chain ◽

Immunoglobulin Level ◽

Exon 2 ◽

Number Of Patients

Abstract Abstract 3958 Background: Recently, a striking example of the effects on acquired somatic mutations in splicing factors such as SF3B1, U2AF1, and SRSF2 has been described. The sequencing of the DNA from abnormal blood cells from patients with several types of leukemia such as AML, CLL, CMML, pre-leukemic syndromes, and MDS, has shown that a high proportion of these cases are associated with somatic mutations in spliceosomal proteins. Also, evidence of cancer-specific alternative splicing and oncogenic somatic mutations in spliceosome subunits has been steadily growing. However, there is not much research regarding aberrant splicing pathways in Multiple myeloma (MM) patients. Therefore, we tried to investigate the presence and prognostic implication of mutation of the SF3B1 and U2AF1 protein in these patients in South Korea. Materials and Methods: We examined a cohort of 87 MM patients and 100 healthy controls for somatic mutations in SF3B1, U2AF1 and SRSF2 by using direct sequencing method. The medical records were reviewed for age, sex, plasma cell percentage, serum M protein, immunoglobulin level, free light chain ratio, calcium, creatinine, hemoglobin, bone lesion, albumin, beta 2 microglobulin, lactate dehydrogenase, treatment outcome, and so on. The collected data was analyzed by SPSS for Windows version 18.0. We performed Pearson's chi-square tests, one way ANOVA analysis, and Student t-test. Survival rates of myeloma patients according to the result of SF3B1, U2AF1 and SRSF2 sequencing were analyzed using Kaplan-Meier log-rank test. Results: Our 87 MM patients showed no mutation including known recurrent ones in SF3B1, U2AF1 and SRSF2 genes. However, the patients displayed 39198T>T/C polymorphism (70.1%) in exon 18 of SF3B1, 8345T>T/G polymorphism (13.8%) in exon 2 of U2AF1 and 5399C/T polymorphism (100%) in exon 1 of SRSF2. In the entire cohort, the number of patients with no polymorphism, one polymorphism, two polymorphisms and three polymorphisms was counted up to 0%, 24.1%, 67.8% and 8.0%, respectively. The T/C polymorphism at position 39198 of SF3B1 exon 18 and the T/G polymorphism at position 8345 of U2AF1 exon 2 were analyzed by allele-specific PCR using normal control. Results in 100 normal controls, polymorphism of SF3B1 exon 18 was taken into account of 82.0%, the remaining is non polymorphism while U2AF1 exon 2 showed 10.0% polymorphism and 90.0% non polymorphism. Sex (p=0.048) and free light chain ratio (p=0.002) showed significant results according to polymorphism status while other clinical characteristics were not associated. The patient with polymorphisms in both SF3B1 and U2AF1 had worse overall survival (P=0.042) and disease-free survival (P<0.01), compared to patients without polymorphism. Conclusion: Our results show no recurrent SF3B1, U2AF1 and SRSF2 mutations in MM patients rather polymorphisms in SF3B1 and U2AF1 gene were significantly implicated in the prediction of poor prognosis. Disclosures: No relevant conflicts of interest to declare.

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Immunoglobulin Heavy/Light Chain Immunoassays for Response Evaluation in Multiple Myeloma: Comparison with Immunofixation, Serum Free Light Chain, and Multicolor Flow- Cytometry

Blood ◽

10.1182/blood.v124.21.3366.3366 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3366-3366 ◽

Cited By ~ 1

Author(s):

Yasuhito Suehara ◽

Keisuke Seike ◽

Kouta Fukumoto ◽

Manabu Fujisawa ◽

Masafumi Fukaya ◽

...

Keyword(s):

Multiple Myeloma ◽

Flow Cytometry ◽

Light Chain ◽

Conflicts Of Interest ◽

Free Light Chain ◽

Multicolor Flow Cytometry ◽

Serum Free ◽

Serum Free Light Chain ◽

Normal Ranges ◽

Best Response

Abstract BACKGROUND: Monitoring of multiple myeloma (MM) patients is required to assess and determine the treatment response. The serum immunoglobulin (Ig) heavy/light chain immunoassays are a new method that enables separate quantification of the different light chain types of each Ig class, i.e., IgGk, IgGl, IgAk, and IgAl. Although the contribution of these tests to disease evaluation has been assessed, available data are still limited. Here, we compared the serum Ig heavy/light chain immunoassays with the conventional methods for disease evaluation. PATIENTS AND METHODS: Three hundred and three samples were obtained from a total of 101 patients with IgG and IgA type MM recruited at Kameda Medical Center and Kanazawa University Hospital. The median age of the patients was 68 years (range: 44 – 89). The median follow-up was 36 months (range: 2.5 – 189.6). The proportions of patients in International Scoring System (ISS) stages I, II, and III were 25%, 35%, and 40%, respectively. Paraprotein type was IgG in 64 patients (44 Gk, 20 Gl) and IgA in 37 (20 Ak, 17 Al). Samples were taken at various times after treatment and analyzed retrospectively with serum Ig heavy/light chain immunoassays (Hevylite®; Binding Site, Birmingham, UK) on a SPAPLUS® turbidimeter. The heavy/light chain ratio (HLCR) was calculated with the Ig' k (either G or A) as the numerator and compared to normal ranges (IgGk:3.84-12.07g/L; IgGl:1.91-6.74g/L; IgGk/IgGl: 1.12-3.21; IgAk:0.57-2.08g/L; IgAl:0.44-2.04g/L; IgAk/IgAl:0.78-1.94). Results were compared to serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE), and serum free light chain immunoassays (FLC). HLC-pair suppression was defined as the uninvolved immunoglobulin of the same isotype 50% below the lower limit of the normal range (IgGk, IgGl, IgAk, IgAl). Residual neoplastic plasma cells (MM-PCs) in bone marrow samples were assessed by multicolor flow cytometry (MFC) simultaneously in 140 samples from 64 patients at very good partial response (VGPR), complete response (CR), and stringent CR (sCR). The MFC negativity was defined at a level of < 10-4 MM-PCs. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan–Meier method, and survival was compared using the log rank test. RESULTS: Myeloma responses were assessed serially after induction therapy and were assigned according to international response criteria. Patients' samples at various responses were: sCR, n = 86 (28%); CR, n = 31 (10%); VGPR, n = 116 (38%); and PR, n = 70 (23%). Normal HLCR was obtained at sCR, CR, and VGPR in 73 (85%), 28 (90%), and 69 (59%) cases, respectively. Discordance in the depth of response between standard electrophoretic methods and HLCR was more commonly seen in IgG compared to IgA MM; possibly reflecting the dose dependent half life of IgG immunoglobulins. In the sera from patients who achieved a CR or better, abnormal HLCR and FLC ratio were seen at rates of 12.8% and 26.5%, respectively. Discordance between normalization of HLCR and FLC ratio was seen in 42% of patients with a CR or better; however, a good correlation between normalization of HLCR and FLC ratio was still observed (Fisher's exact test, P = 0.004). Among the 71 sera from patients with a CR or better in which simultaneous MFC data were available, 16 (22.5%) sera were MFC-negative. Among the patients who achieved a VGPR or better, patients with a normal HLCR had fewer MM-PCs than those with an abnormal HLCR (median 9.8x10-4vs. 46.0x10-4, respectively, P=0.062), although the difference was not statistically significant. Abnormal HLCR in CR samples was seen more frequently in patients with IgA type (19%) than IgG type (7.7%). Longer PFS and OS were observed in patients who achieved HLCR normalization at best response than in those who did not (PFS; 83.8 months vs. 41.8 month, respectively, P = 0.016 and OS; not reached vs. not reached, P = 0.018). When patients at best response were divided into with or without uninvolved HLC pair suppression, the latter group showed significantly better OS compared to the former group (not reached vs. not reached, P=0.019). CONCLUSIONS: The findings presented here suggest the potential usefulness of heavy/light chain immunoassays for monitoring of myeloma response in patients with IgA myeloma and residual MM-PC assessment at VGPR or better. Presence of abnormal HLCR at best response and HLC pair suppression were also associated with poorer survival. Disclosures No relevant conflicts of interest to declare.

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P1114HA-130 HEMOPERFUSION CARTRIDGE IN THE TREATMENT OF CAST NEPHROPATHY IN A 58-YEAR-OLD MALE WITH MULTIPLE MYELOMA: A CASE REPORT

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1114 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Joanna Margarita Santos ◽

Maria Kristina L Alolod

Keyword(s):

Multiple Myeloma ◽

Renal Failure ◽

Case Report ◽

Light Chain ◽

Free Light Chain ◽

Light Chains ◽

Serum Free ◽

Serum Free Light Chain ◽

Cast Nephropathy ◽

History Of

Abstract Background and Aims Multiple myeloma is a plasma cell neoplasm that results in the production of monoclonal immunoglobulin. Renal failure is a common complication of multiple myeloma, occurring in approximately one-half of patients on initial presentation and is associated with increased mortality. Cast nephropathy in particular, is considered to be one of the major mechanisms of renal failure in multiple myeloma, and is characterized by precipitation of free light chains in the distal nephron, leading to intratubular obstruction, inflammation and fibrosis. Recent studies have demonstrated the use of extracorporeal methods such as plasmapheresis and high-cutoff membrane dialysis as an adjunctive therapy to chemotherapy in the management of cast nephropathy, however currently there are no existing guidelines in the use of extracorporeal therapies in the management of complications of multiple myeloma. Hemoperfusion is an extracorporeal treatment technique which utilizes adsorption in the removal of specific toxins. The HA 130 cartridge in particular has a resin pore size distribution of 500Da- 40 KDa and is able to remove molecules at 5-30kDa. In this case report we describe the use of HA 130 hemoperfusion cartridge in the treatment of cast nephropathy in Multiple Myeloma. Method A 58-year-old male, diabetic, non-hypertensive came in for 5-day history of generalized body weakness, associated with myalgia, lumbar pain and undocumented fever, with 1-day history of loose stools and vomiting. Upon admission blood tests done revealed anemia with a hemoglobin of 7.8g/dl, creatinine of 9.97mg/dL and potassium of 5.5mmol/L. He was diagnosed with acute renal failure and underwent hemodialysis on the second hospital day. On workup he had lytic bone lesions in the spine, pelvis and cranium on CT scan and x-ray. Serum Protein Electrophoresis (SPEP) and Serum Free Light Chain (sFLC) tests showed a monoclonal gammopathy. Serum beta 2 microglobulin was elevated at 12,618ng/ml. Free kappa and lambda light chains were also elevated at 19,250mg/L and 25.7mg/L, respectively. Bone marrow biopsy was done, with findings of markedly hypercellular marrow with 80% plasma cells confirming the diagnosis of Multiple Myeloma. Combined hemodialysis with hemoperfusion were done using HA 130 filter and hi flux dialyzer for 2.5 hours then hemodialysis for three times a week. Patient was also started on chemotherapy using Bortezomib with Dexamethasone for 2 cycles. Results Patient had a total of 14 sessions of combined hemoperfusion with hemodialysis. On repeat free kappa light chains decreased to 212.5mg/L. Patient was maintained on hemodialysis three times a week and was discharged after 55 hospital days. Outpatient hemodialysis was continued three times a week, and after 2 weeks, patient showed signs of renal recovery with a repeat creatinine of 2.1mg/dL. Four weeks after discharge, patient was independent of hemodialysis with a repeat creatinine of 1.3mg/dL. Conclusion This report highlights the use of hemoperfusion using HA 130 cartridge in combination with chemotherapy using Bortezomib in reducing free light chain levels in a 58-year-old male that developed renal failure secondary to cast nephropathy. Patient was able to achieve reduction in free light chain levels, improvement in renal function and eventually independence from hemodialysis four weeks after the last hemoperfusion treatment. Further studies using a randomized control trial on the use of hemoperfusion in directly reducing serum free light chain levels is recommended. The value of hemoperfusion on the rate of independence from hemodialysis, as well as survival rates among patients with renal failure secondary to multiple myeloma may also be worth investigating using larger studies.

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Role of Free Light Chain Assay Ratio to Distinguish Between CR According EBMT Criteria or Stringent Complete Remission (sCR) According IMWG in Multiple Myeloma Patients.

Blood ◽

10.1182/blood.v114.22.1787.1787 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1787-1787

Author(s):

Svetlana Asenova ◽

Ulrike Bacher ◽

Andreas Gerritzen ◽

Axel R. Zander ◽

Nicolaus Kröger

Keyword(s):

Multiple Myeloma ◽

Complete Remission ◽

Light Chain ◽

Partial Remission ◽

Conflicts Of Interest ◽

Free Light Chain ◽

Normal Range ◽

Light Chain Immunoglobulin ◽

Definition Of ◽

Additional Value

Abstract Abstract 1787 Poster Board I-813 Introduction The qualitative assay for free light chain has been reported to be sensitive and specific for detecting and monitoring diseases caused by monoclonal gammopathies such as multiple myeloma. More recently the International Myeloma Working Group proposed uniform response criteria including a new definition of stringent complete remission (sCR). The definition of stringent complete remission requires beside absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence also normalization of free light chain ratio in serum. Patients and Methods We evaluate the value of free light chain assay to determine stringent CR by monitoring 87 patients with multiple myeloma who achieved complete remission (n=52) or very good partial remission (n=35) between January 2003 and December 2008. Free light chain measurements were performed with the commercially available Free liteTM Kit (Binding Site, Heidelberg, Germany). Because of the shorter half-life of free light chain assay ratio, only patients were included, if the complete or very good partial remission remains stable for at least 3 months. The comparison between immunofixation and free light chain ratio was performed at least 6 weeks after immunofixation becomes negative for the first time. 87 patients (50 mal and 37 female) were included, 67 had intact immunoglobulin and 11 had light chain immunoglobulin at time of diagnosis. The remission status was determined either after allogeneic (n = 73) or autologous (n = 7) stem cell transplantation or after conventional bortezomib or lenalidomide containing chemotherapy (n = 7). Results 35 out of 87 patients achieved a very good partial or near complete remission with still positive immunofixation. In 22 out of those 35 patients the free light chain kappa ratio was within the normal range of 0.26 – 1.65 mg/l (63 %). Only in 13 patients with persistent immunofixation positivity the free light chain ratio was outside the normal range (37%). 52 patients achieved complete remission according to the EBMT criteria with negative immunofixation for at least 3 months. In those patients all (100 %) had a normal free light chain kappa/lambda ratio. In a subgroup of patients (n = 10) who relapsed during follow-up from complete remission sequential monitoring of immunofixation and free light assay was performed as recently described [4]. In 9 out of 10 patients a free light chain ratio became abnormal at a median 90 days before immunofixation became positive. Conclusions The free light chain assay ratio is a useful marker for a faster detection of remission or progression in myeloma patients. However, these results do not support additional value of free light chain ratio to determine the depth of remission in immunofixation negative patients. More sensitive methods such as imunophenotyping analysis by FACS or molecular primer should be used to determine depth of complete remission since these methods have shown relevant clinical impact. Disclosures No relevant conflicts of interest to declare.

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Autologous Haematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma Complicated By Dialysis-Dependent Renal Failure

Blood ◽

10.1182/blood-2018-99-115880 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5765-5765

Author(s):

Maiia V. Firsova ◽

Larisa P. Mendeleeva ◽

Irina G. Rekhtina ◽

Maxim V. Solovev ◽

Olga S. Pokrovskaya ◽

...

Keyword(s):

Multiple Myeloma ◽

Renal Failure ◽

Conflicts Of Interest ◽

Survival Rates ◽

Progression Free Survival ◽

Treatment Method ◽

High Rate ◽

Haematopoietic Stem Cell ◽

Post Transplantation ◽

Renal Response

Abstract Introduction. Multiple myeloma (MM) in its early onset is complicated by myeloma nephropathy in 20-30% of patients, 10% of whom require haemodialysis. Early studies have shown that renal dysfunction has no adverse effect on melphalan pharmacokinetics. Auto-HSCT in some patients allows to restore renal function and to stop hemodialysis. Aim of the study. To assess the safety and efficacy of auto- HSCT in MM patients with dialysis-dependent renal failure. Materials and methods. During a period from May 2010 to December 2016 thirteen (3 males, 10 females) MM patients with dialysis-dependent renal failure aged 48 to 65 years (median 58) underwent auto-HSCT. The diagnosis was made according to IMWG criteria. In the onset of the disease, the median creatinine level was 1091 μmol /L, and GFR (CKD-EPI) ranged 3 to 10 ml / min / 1.73 m2 (median 3). Induction therapy included bortezomib-containing regimens in all patients, bendamustine was used in 5 (38.5%) patients, immunomodulatory drugs were used in 2 (15%) patients. HSC mobilization was performed according to the scheme: G-CSF 10 μg/kg. The median number of harvested CD34+ cells was 3.46x106/kg. Subsequently, against the background of programmed hemodialysis and in the setting of high-dosed melphalan (100-200 mg/m2), 12 patients underwent a single and one patient underwent a tandem auto-HSCT. On Day 100 after auto-HSCT, an antitumor response and renal response were assessed. Survival curves were constructed using the Kaplan-Meier method. Statistical analysis was done using Statistica 10. Results. Before auto-HSCT CR was documented in 8 (61%) patients, VGPR was documented in 4 (31%) patients, PR was documented in 1 (8%) patient, with no renal response registered, GFR: 4-10 ml/min/1.73 m2 (median 5). The period of agranulocytosis after auto-HSCT was accompanied by infectious complications, cardiac and neurological dysfunctions (Table 1). The resulting complications were stopped; the mortality associated with transplantation (TRM) was 0%. At +100 days after auto-HSCT, the PR was confirmed in 9 (70%) patients and VGPR was confirmed in 4 (30%) patients. GFR: 5 - 17 ml/min/1.73 m2 (median 7). The minimal renal response was registered in 2 patients (15%), hemodialysis was stopped. After a median follow-up of 52 months 5-year progression-free survival (PFS) was 71%, and OS was 92%. Conclusion. Auto-HSCT in MM patients with dialysis-dependent renal failure is a feasible and effective treatment method, nevertheless, characterized by a high rate of early post-transplantation complications. Dialysis-dependent renal failure is not a contraindication for the use of high dosed melphalan followed by auto-HSCT. The probability of hemodialysis discontinuation after auto-HSCT was 15%. Survival rates are comparable to those in patients without renal impairment. Disclosures No relevant conflicts of interest to declare.

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Clinical Significance of Serum Free Light Chain Test in the First Onset of Multiple Myeloma

Blood ◽

10.1182/blood.v120.21.4999.4999 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4999-4999

Author(s):

Pan Hong ◽

Xiaojian Meng ◽

Jingsong He ◽

Wenjun Wu ◽

Yi Li ◽

...

Keyword(s):

Multiple Myeloma ◽

Survival Analysis ◽

Clinical Significance ◽

Light Chain ◽

Conflicts Of Interest ◽

Free Light Chain ◽

Serum Free ◽

Serum Free Light Chain ◽

Sensitivity Assessment ◽

First Onset

Abstract Abstract 4999 Objective: Clinical significance of serum free light chain (sFLC) test in the diagnosis, efficacy evaluation, prognosis judgment of first onset of multiple myeloma (MM). Method: Medical records of 39 cases of first-onset MM were gathered in our hospital from 1/2010 to 2/2012, including 25 male and 14 female patients with the median age being 63 years old. sFLC-kappa and sFLC-lambda were determined by immune turbidimetric assay, sFLC-kappa/lambda were calculated and the results were compared with that of immunofixation electrophoresis (IFE) as well as serum protein electrophoresis (SPE) for sensitivity assessment. All patients were treated with chemotherapy followed by sFLC detection and efficacy assessment. Patients with a sFLC results higher than median were marked as high-sFLC, the rest were marked as low-sFLC, and survival analysis were made comparing the two groups. Results: Of the 39 first-onset MM patients, 38 were detected as sFLC- kappa/lambda positive, that's a sensitivity of 97. 4%, higher than IFE (79. 5%), SPE (53. 8%), and uPE (38. 5%). As condition improves after treatment, sFLC gradually decline and sFLC- kappa/lambda level falls back to normal. Evaluation of efficacy by sFLC results has an accuracy of 77. 27%, significantly higher than that of corresponding M protein test£̈ P=0. 009£©. Follow-up survival analysis showed that the OS time and TTP time of low-sFLC group are significantly higher than those of high-sFLC group (P=0. 037, 0. 009 respectively). Conclusion: sFLC detection is a highly sensitive quantitative method, can help the diagnosis of MM, gives a quicker assessment of treatment efficacy, and can predict disease recurrence. When it's the first onset, sFLC level can also roughly forecast the prognosis. Disclosures: No relevant conflicts of interest to declare.

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