Lambda Light Chain Multiple Myeloma in a Patient with Primary Biliary Cholangitis: Association or Mere Coincidence?

Cutaneous involvement of multiple myeloma (MM) is uncommon, typically occurs in late stage disease, and is a poor prognostic indicator with an approximate eight month median survival. We present a 51-year-old man with relapsed lambda light chain MM who developed abrupt asymptomatic skin metastases. Biopsy revealed a dermis replete of atypical plasma cells, positive for CD138 and CD45. In situ hybridization confirmed lambda light chain restriction. Despite rescue antimyeloma therapy with the anti-CD38 drug daratumumab, he rapidly declined clinically and succumbed to the disease four weeks after presentation. A standard treatment approach for cutaneous MM does not currently exist; however, various techniques to detect cytogenetic abnormalities are emerging and will provide additional prognostic value and direct individualized therapy.

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Marked efficacy of rituximab in two patients with Waldenstrom macroglobulinemia-like multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e18548 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e18548-e18548

Author(s):

Christoph J. Heuck ◽

Saad Zafar Usmani ◽

Erming Tian ◽

Qing Zhang ◽

Frits Van Rhee ◽

...

Keyword(s):

Multiple Myeloma ◽

Light Chain ◽

Plasma Cells ◽

Single Agent ◽

Organ Damage ◽

Detailed Examination ◽

Lambda Light Chain ◽

Waldenström Macroglobulinemia ◽

Waldenstrom Macroglobulinemia ◽

First Case

e18548 Background: Rituximab (R) has been deemed to be ineffective in multiple myeloma (MM), despite CD20 expression in 10-15% of MM. Here we report two cases, selected by a genomic approach, with an excellent response to single agent R. Methods: as below Results: Patient 1: A 49 yr old male with IgG lambda MM with 80% bone marrow (BM) plasma cells (PC) and IgG level of 23 g/L had been treated elsewhere with one cycle of CRD. Here, we noted CD-2 subclass by gene expression profilin (GEP), however without spiked expression of CCND1 and CCND3 genes as manifestation of a t[11:14] or a t[6:14]. GEP further revealed a del 6q and overexpression of EBI2, both commonly seen in Waldenstrom Macroglobulinemia (WM). All findings were confirmed by FISH. Unsupervised clustering in the context of MGUS, untreated MM and WM-PC, confirmed WM-like MM in this patient. Sole therapy with R (750 mg/m2/d x 5d, weekly x 4, bi-weekly x 4 and then monthly) resulted in a reduction of IgG from 1850 mg/dL to 950 mg/dl and BM PC from 60% to 10% at 9 months and a decrease in sLFLC from 68 mg/dL to 10 mg/dL at 12 months follow up. Patient 2: Based on the above observation, we identified a second patient. This 37-yr old male had been diagnosed with lambda light chain MM 42 months earlier with a BM PC of 15%, lambda light-chain proteinuria of 1.9 g/d and sLFLC in the 200mg/dL range. Because of absence of CRAB criteria, he was followed expectantly. Rising BM PC to 50% and concern for end-organ damage motivated a detailed examination of GEP data. GEP showed high expression of CD20 and EBI2 and absence of CCND1 and CCND3 spikes. This was confirmed by FISH, which also revealed a del 6q. As in the first case, this patient co-segregated with WM. R treatment on the same schedule resulted in a reduction of sLFLC levels from 249 mg/dL to 29.9 mg/dl and of Bence Jones proteinuria from 1766 mg/d to 242 mg/d. Conclusions: The presumed lack of activity of R in MM needs to be revisited in light of the marked response noted in these 2 patients. Studies are in progress (a) to extend R therapy to similar cases, and (b) to more fully characterize the prevalence of genetic/phenotypic characteristics, as seen in these 2 cases, among several thousand MM patients. This updated information will be presented at the meeting.

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Triphenotypic multiple myeloma expressing kappa or lambda light chain or both

British Journal of Haematology ◽

10.1111/bjh.12100 ◽

2012 ◽

Vol 160 (1) ◽

pp. 4-4 ◽

Cited By ~ 2

Author(s):

Yang Liu ◽

Yan Zhang ◽

Weidong Han

Keyword(s):

Multiple Myeloma ◽

Light Chain ◽

Lambda Light Chain

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A Prospective Observational Study of Clinico-Pathological Features, Prognostic Factors and Treatment Response to Primary Therapy in Multiple Myeloma at a Tertiary Care Centre

Blood ◽

10.1182/blood-2019-125752 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5559-5559

Author(s):

Saurabh Mishra ◽

Ashok K Vaid ◽

Nitin Sood ◽

Manorama Bhargava ◽

Bhuvan Chugh ◽

...

Keyword(s):

Multiple Myeloma ◽

Treatment Response ◽

Light Chain ◽

Prospective Observational Study ◽

Tertiary Care ◽

High Dose ◽

Primary Therapy ◽

Lambda Light Chain ◽

Tertiary Care Centre ◽

Cell Support

Title: "A prospective observational study of clinico-pathological features, prognostic factors and treatment response to primary therapy in Multiple Myeloma at a tertiary care centre" Background: Multiple myeloma (MM) is characterised by the neoplastic proliferation of plasma cells leading to excess monoclonal immunoglobulins. The incidence of multiple myeloma in India ranges from 1.2 to 1.8 per 100,000. There is paucity of cytogenetic data from this part of subcontinent. The aim of our study is to report various clinicopathological features, evaluate biological markers of prognostication including cytogenetic variables and assess treatment response after standard primary therapy. Methods and Materials: The study was carried out at a tertiary care center in Northern India. After final diagnosis of multiple myeloma was established, each patient was risk stratified via FISH cytogenetic analysis as per the revised ISS. Definitive management plan was individualised, including assessment for high dose therapy with peripheral blood stem cell support. Treatment response were recorded as per standard IMWG response criteria. Significant toxicities associated with treatment were also recorded. Results: Eighty consecutive patients with newly diagnosed multiple myeloma were enrolled prospectively from April 2017 to November 2018. The median age at diagnosis was 63 years, and number of males & females were equal. The most common presenting symptom was back pain (67.8 % patients) and most frequent clinical sign was pallor (86.4 %). All four CRAB features were documented only in 16.9% patients. M-Band was present in 96.6% patients and on SFLC assay 59.3% and 40.7% were kappa and lambda light chain restricted respectively. Most common heavy chain abnormality detected was IgG. Seventy percent patients had lytic lesions on imaging while only 3% suffered skeletal related events. Cytogenetic evaluation by interphase FISH was carried out in all patients upfront. No chromosomal abnormality was documented in 61.25 % while among those with chromosomal abnormalities, most commonly detected was del13q14.3 (23.75 %). Overall, 66.6% patients were stratified as standard risk, 28.1% as intermediate risk and only 3 (5.3%) patients were categorised as high risk. Most common induction regimen was VRD. Overall response rate was 94.9 % and VGPR or better responses were observed in 77.9% patients. Most common adverse effect of therapy was peripheral neuropathy of all grades. Of the 77 patients who completed primary therapy, 21.4% patients underwent high dose therapy with peripheral blood stem cell support while 67.7% patients were started on maintenance therapy. Four (5.1 %) non-responder was started on 2nd line treatment. On univariate analysis, higher deeper responses (VGPR or better) were observed in patients with IgA & IgG related myeloma and better overall response rates were seen in IgG related myeloma. Those with kappa light chain myeloma had 5.67 times higher likelihood of achieving response as compared to lambda light chain myeloma. Also, patients with kappa light chain myeloma achieved higher VGPRs as compared to lambda light chain myeloma. There was 17 times high risk of non-response in the presence of local bony tenderness. None of the findings were found to be significant on multivariate analysis. Conclusions: Use of interphase FISH to identify various cytogenetic markers help in stratification & staging of the disease which in turn act as a marker for prognostication. They should be a part of standard care in multiple myeloma. In majority we could administer treatment in accordance to standard practice guidelines and response rates were similar to those reported my seminal studies. Our study in a longer follow up will yield some useful information which will help in the better care of the patients. Disclosures No relevant conflicts of interest to declare.

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Multıple Myeloma wıth Homogenous Secretıon of Lambda Lıght Chaın Immunoglobulın: A Case Report

British Journal of Medicine and Medical Research ◽

10.9734/bjmmr/2016/25188 ◽

2016 ◽

Vol 14 (10) ◽

pp. 1-7

Author(s):

J Olaniyi ◽

P Ogundeji

Keyword(s):

Multiple Myeloma ◽

Case Report ◽

Light Chain ◽

Immunoglobulin A ◽

Lambda Light Chain ◽

Light Chain Immunoglobulin

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IgD Myeloma: Clinical Features and Outcome In The Era Of Novel Agents

Blood ◽

10.1182/blood.v122.21.1935.1935 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1935-1935 ◽

Cited By ~ 1

Author(s):

Flora Zagouri ◽

Efstathios Kastritis ◽

Argiris S. Symeonidis ◽

Nikolaos Giannakoulas ◽

Eirini Katodritou ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Renal Dysfunction ◽

Light Chain ◽

The Other ◽

Novel Agents ◽

Primary Therapy ◽

Lambda Light Chain ◽

Prognostic Features ◽

High Risk Disease

Abstract IgD multiple myeloma is a rare variant of the disease and in various series accounts for about 2% of patients with symptomatic myeloma. It has been suggested that patients with IgD myeloma may have an inferior outcome when compared to other patients. However, data on IgD myeloma patients treated in the novel agent era are lacking. In order to assess the frequency and evaluate the outcome and the specific characteristics of patients with IgD myeloma we analyzed the database of the Greek Myeloma Study Group to identify such patients. Between January 2000 and December 2012, among the 1239 patients with previously untreated, symptomatic, myeloma, 31 patients (2.5%) were diagnosed with IgD myeloma. Of interest, 84% of patients with IgD myeloma had lambda light chain (versus 38% of the patients with other subtypes of MM, p<0.001). The median age of patients with IgD myeloma was 65 years (range 26-80 years) versus 68 years (range 23-96 years) for patients with other subtypes of MM (p=0.073), while 10% of patients with IgD versus 28% of the other patients were >65 years (p=0.023) and 10% of patients with IgD versus 3.8% of the other patients were ≤40 years of age. Patients with IgD myeloma presented more often with significant renal dysfunction (serum creatinine ≥2 mg/dl in 52% versus in 19%, p<0.001 or eGFR <30 ml/min/1.73m2 in 42% versus 18% in patients of other subtypes, p=0.001) and excreted larger amounts of Bence Jones protein (59% excreted ≥2 gr per day versus 17% of the other patients, p<0.001). Patients with IgD myeloma had also more often features of high risk disease including ISS-3 disease (60% versus 37% for the other patients, p=0.011) and elevated serum LDH (≥300 IU/L) in 29% versus10% of the other patients (p=0.001). Response to primary therapy for patients with IgD myeloma was similar to other patients (at least PR in 77% versus 72% respectively), although there was a trend for better quality of responses in patients with IgD myeloma (sCR and CR in 26% versus 15% of patients, and at least VGPR in 53% versus 29% in patients of other subtypes, respectively, p=0.059). However, more patients with IgD myeloma had received primary therapy with bortezomib-based regimens (40% versus 22%) and less often IMiD-based therapy (20% versus 35%), while similar proportions of patients received conventional chemotherapy-based regimens (40% versus 44%; p=0.043). Despite the increased frequency of features of high risk disease in patients with IgD myeloma, the median survival of these patients was 51.5 months versus 50.7 months for patients of other subtypes (p=0.850). In a multivariate model to adjust for differences in prognostic features, IgD myeloma was not associated with a different prognosis. We also compared the outcome of patients with IgD myeloma treated before and after January 1st, 2000. The survival of the patients with IgD myeloma who started therapy before versus after 2000 was 44 months (p=0.018). In conclusion, in a large series of patients with symptomatic multiple myeloma, the incidence of IgD myeloma is 2.5%. The vast majority of patients with IgD myeloma is associated with lambda light chain and present more often with significant Bence Jones proteinuria, significant renal dysfunction and features of advanced disease. However, their outcome in the era of novel agents is similar to that of patients with other myeloma subtypes. Disclosures: No relevant conflicts of interest to declare.

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In multiple myeloma, clonotypic B lymphocytes are detectable among CD19+ peripheral blood cells expressing CD38, CD56, and monotypic Ig light chain [published erratum appears in Blood 1995 Jun 1;85(11):3365]

Blood ◽

10.1182/blood.v85.2.436.436 ◽

1995 ◽

Vol 85 (2) ◽

pp. 436-447 ◽

Cited By ~ 112

Author(s):

PL Bergsagel ◽

AM Smith ◽

A Szczepek ◽

MJ Mant ◽

AR Belch ◽

...

Keyword(s):

Multiple Myeloma ◽

B Cells ◽

Light Chain ◽

Late Stage ◽

Plasma Cells ◽

Surface Expression ◽

Lambda Light Chain ◽

Cdr3 Region ◽

Polymerase Chain ◽

Ig Heavy Chain

Abstract Multiple myeloma (MM) is characterized by a plasma cell infiltrate of the bone marrow (BM). However, late-stage monotypic B cells have been detected in the blood. This work analyzes the effects of clinical treatment on late stage CD19+ B cells present in 752 blood samples from 152 MM patients. MM patients have 2 to 8 times as many circulating CD19+ cells as do normal donors. Analysis of the Ig heavy chain (IgH) gene rearrangements using polymerase chain reaction indicates that the CD19+ population includes cells sharing the same clonotypic CDR3 region as is detected in the BM plasma cells, for patients analyzed during chemotherapy or in relapse. They are also monotypic as defined by their cytoplasmic or surface expression of Ig kappa or lambda light chain. The light chain restriction is the same as that of the BM plasma cells. Individual patients observed over 1- to 2-year periods exhibit considerable variation in the number of B cells present in blood; this number does not correlate with the concentration of serum monoclonal Ig. The monoclonal blood CD19+ cells are not eliminated by any of the chemotherapy regimens analyzed and remain at high levels during transient remissions. Patients in the progressive phase of disease or in relapse have significantly higher numbers of B cells than do patients in transient remission or untreated patients. During periods when the quantity of blood B cells approaches normal, phenotypically their quality is highly abnormal, with physical and phenotypic heterogeneity. Most B cells express CD45R0, a high density of CD38, and CD56 characteristic of late-stage B or pre-plasma cells. CD38hi blood B cells had a cyclical presence. We conclude that monoclonal B cells in the blood of myeloma patient populations include drug-resistant reservoirs of clonotypic cells that may underlie relapse.

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Lambda light chain multiple myeloma presenting as pleural mass

Respiratory Medicine CME ◽

10.1016/j.rmedc.2010.01.007 ◽

2011 ◽

Vol 4 (1) ◽

pp. 12-14

Author(s):

Mohammad Shameem ◽

Jamal Akhtar ◽

Rakesh Bhargava ◽

Zuber Ahmad ◽

Ummul Baneen ◽

...

Keyword(s):

Multiple Myeloma ◽

Light Chain ◽

Lambda Light Chain

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In multiple myeloma, clonotypic B lymphocytes are detectable among CD19+ peripheral blood cells expressing CD38, CD56, and monotypic Ig light chain [published erratum appears in Blood 1995 Jun 1;85(11):3365]

Blood ◽

10.1182/blood.v85.2.436.bloodjournal852436 ◽

1995 ◽

Vol 85 (2) ◽

pp. 436-447 ◽

Cited By ~ 7

Author(s):

PL Bergsagel ◽

AM Smith ◽

A Szczepek ◽

MJ Mant ◽

AR Belch ◽

...

Keyword(s):

Multiple Myeloma ◽

B Cells ◽

Light Chain ◽

Late Stage ◽

Plasma Cells ◽

Surface Expression ◽

Lambda Light Chain ◽

Cdr3 Region ◽

Polymerase Chain ◽

Ig Heavy Chain

Multiple myeloma (MM) is characterized by a plasma cell infiltrate of the bone marrow (BM). However, late-stage monotypic B cells have been detected in the blood. This work analyzes the effects of clinical treatment on late stage CD19+ B cells present in 752 blood samples from 152 MM patients. MM patients have 2 to 8 times as many circulating CD19+ cells as do normal donors. Analysis of the Ig heavy chain (IgH) gene rearrangements using polymerase chain reaction indicates that the CD19+ population includes cells sharing the same clonotypic CDR3 region as is detected in the BM plasma cells, for patients analyzed during chemotherapy or in relapse. They are also monotypic as defined by their cytoplasmic or surface expression of Ig kappa or lambda light chain. The light chain restriction is the same as that of the BM plasma cells. Individual patients observed over 1- to 2-year periods exhibit considerable variation in the number of B cells present in blood; this number does not correlate with the concentration of serum monoclonal Ig. The monoclonal blood CD19+ cells are not eliminated by any of the chemotherapy regimens analyzed and remain at high levels during transient remissions. Patients in the progressive phase of disease or in relapse have significantly higher numbers of B cells than do patients in transient remission or untreated patients. During periods when the quantity of blood B cells approaches normal, phenotypically their quality is highly abnormal, with physical and phenotypic heterogeneity. Most B cells express CD45R0, a high density of CD38, and CD56 characteristic of late-stage B or pre-plasma cells. CD38hi blood B cells had a cyclical presence. We conclude that monoclonal B cells in the blood of myeloma patient populations include drug-resistant reservoirs of clonotypic cells that may underlie relapse.

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