Management of light chain deposition disease: A systematic review.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20042-e20042
Author(s):  
Adeel Masood ◽  
Moazzam Shahzad ◽  
Ahsan Wahab ◽  
Pranali Santhoshini Pachika ◽  
Tehniat Faraz Ahmed ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Retrospective Studies ◽  
Case Reports ◽  
Single Agent ◽  
Case Series ◽  
Cell Transplant ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Light Chain Deposition

e20042 Background: Light-chain deposition disease (LCDD) is part of a wide spectrum of plasma cell proliferation disorders. LCDD predominantly affects kidneys by systemic deposition of congo red negative non-fibrillar light chains. Due to the rarity of disease, no prospective data is available, and clear guidelines don’t exist for the treatment. We reviewed data to summarize effective treatment strategies. Methods: A literature search was conducted on PubMed, Cochrane, and ClinicalTrials.gov with final update in November 2020 using terms ‘light chain deposition disease’, ‘therapy,’ and ‘disease management’. Library was manually screened to remove articles on LCDD in transplant kidneys. We identified 63 case reports/series and 11 retrospective studies n=365. Results: Retrospective Studies: 9 studies (n=283) identified various combinations of LCDD and plasma cell dyscrasias given the rarity of idiopathic LCDD. Lorenz et al. reported 6 patients (pts) that received ASCT with MEL preconditioning with 92% improved proteinuria and 95% improved eGFR. Pozzi et al. reported 63 pts (32% idiopathic LCDD, 65% concurrent MM and 3% concurrent CLL) where all pts received a combination of vincristine, doxorubicin, dexamethasone/methylprednisolone. 5/63 patients received ASCT. The median survival was 4.1 years. Bortezomib (V) based regimens: Most experts favor V based regimens to treat LCDD, but no dedicated trials exist. 26 case reports/case series (37 pts) included; 23 pts with idiopathic LCDD and rest with a concurrent disorder. Daratumumab: Milani et al. treated 8 pts with LCDD and concurrent MM with single agent daratumumab who failed at least one regimen. Autologous stem cell transplant (ASCT): 13 case reports/case series (20 pts) identified who received ASCT with melphalan (MEL) conditioning with/without various combinations of chemotherapies before and after ASCT. 14 pts had LCDD, and 6 pts had concurrent clonal cell dyscrasia. Miscellaneous regimens: Various other regimens showed promising results with improved renal functions but not well studied e.g., thalidomide and dexamethasone (Haruyuki et al.). Conclusions: Dedicated clinical trials are difficult given rarity of LCDD but needed. Bortezomib based regimens seem to be good options, ASCT with MEL conditioning is a suitable choice for younger and fit pts.[Table: see text]

scholarly journals Hematologic Responses in Patients with Heavily Pretreated Light Chain Deposition Disease (LCDD) Receiving Daratumumab

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1985-1985
Author(s):  
Paolo Milani ◽  
Marco Basset ◽  
Andrea Foli ◽  
Giampaolo Merlini ◽  
Giovanni Palladini
Keyword(s):  
Partial Response ◽  
Light Chain ◽  
Cell Transplant ◽  
Light Chain Deposition Disease ◽  
Hematologic Response ◽  
Deposition Disease ◽  
Heavily Pretreated ◽  
Renal Progression ◽  
Line Of Therapy ◽  
Light Chain Deposition

Abstract Introduction: The monoclonal antibody daratumumab showed high response rates and a good safety profile in multiple myeloma and is being evaluated in clinical trials in AL amyloidosis. Light chain deposition disease (LCDD) is a rare monoclonal gammopathy of renal significance. Treatment directed against the underlying plasma cell clone can prevent renal progression. Bortezomib is commonly used upfront in these patients and daratumumab may represent a powerful novel option. Methods: We report the outcome of six patients with refractory light chain deposition disease (LCDD) treated with daratumumab at the Amyloidosis Research and Treatment Center of Pavia. All patients gave written informed consent. Hematologic response was assessed according to the International Society of Amyloidosis criteria. Results: Six patients (5 males and 1 female) received daratumumab intravenously at 16 mg/kg weekly for 8 weeks, followed by every other week infusions for 8 doses and then monthly infusions. Patients' clinical characteristics are reported in Table 1. All patients received daratumumab single agent except one who was treated with daratumumb and bortezomib combination (this patient received only 1 prior line of therapy). All patients were refractory to the last line of therapy. All patients received at least two months of therapy. All patients were previously treated with bortezomib, pomalidomide was used in 4 cases, lenalidomide, thalidomide and bendamustine in 2 cases each, and autologous stem cell transplant was performed in 4 subjects. The median time from LCDD diagnosis to daratumumab initiation was 8.3 years (range 8 - 147 months). Five of the 6 patients obtained hematologic response with at least a reduction of 50% of the dFLC value (partial response). Three patients obtained a very good partial response (dFLC <40 mg/L). The estimated glomerular filtration rate improved in one subject (from 30 to 45 mL/min per 1.73 m2) and in all the others remained stable. In 2 subjects treatment was temporarily discontinued due to pneumonia. Conclusions: This is the first report of the use of daratumumab in LCDD. This antibody yielded rapid and significant hematologic responses in five of six heavily pretreated patients with this disease, preventing renal progression. Daratumumab represents a promising option for these patients and larger, international studies are warranted. Disclosures Merlini: Akcea: Consultancy; Ionis: Consultancy; Prothena: Consultancy; Millenium: Consultancy; Janssen: Consultancy; Pfizer: Consultancy. Palladini:Celgene: Other: Travel support; Janssen: Membership on an entity's Board of Directors or advisory committees; Prothena: Honoraria.

Bortezomib-Dexamethasone As Induction Therapy for Light Chain Deposition Disease (LCDD): A Single Center Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5027-5027
Author(s):  
Federica Lessi ◽  
Monica Castelli ◽  
Livio Trentin ◽  
Sara Altinier ◽  
Francesco Piazza ◽  
...  
Keyword(s):  
Renal Function ◽  
Stem Cell ◽  
Plasma Cell ◽  
Induction Therapy ◽  
Light Chain ◽  
High Dose ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Osteolytic Bone Disease ◽  
Light Chain Deposition

Abstract Abstract 5027 Background: LCDD is a rare plasma cell dyscrasia characterized by deposition of immunoglobulin light chain in kidneys and, occasionally, in other organs such as liver and heart. Most patients present with rapidly deteriorating renal function and nephrotic proteinuria. There is no standard treatment for LCDD. High dose dexametasone (HDD) with or without alkylating agents and high dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) have been used, the latter with better results. Recently the combination therapy with Bortezomib-Dexametasone (BD) has been used in small series of patients and has shown promising results. Here we report on four patients with LCDD treated in our center from September 2010 to September 2011 with BD as induction therapy. Patients and Methods: The characteristics of the patients are shown in Table 1. Three patients were male; the median age was 44. 5 years (range 37–64 years). Two patients had more than 20% bone marrow plasma cell count with no evidence of active multiple myeloma (MM) defined by osteolytic bone disease, hypercalcemia or myeloma cast nephropaty. All patients had renal biopsy with histologic and immunofluorescence studies. In all patients except one, the diagnosis was confirmed by electron microscopy examination. One patient was therapy naive and three patients were refractory to HDD. All patients but one presented with impaired renal function and all of them showed nephrotic albuminuria. Serum free light chains values (sFLC) were high in all patients, with abnormal kappa to lambda ratio (R k/λ). Noteworthy, in three patients serum immunofixation electrophoresis did not succeed in detecting the circulating monoclonal light chain. Patients were given Bortezomib (1. 3 mg/m2days 1, 4, 8 and 11) and Dexamethasone (40 mg days 1–4) every 21 days, for three to six cycles. Results: Two patients achieved normalization of R k/λ. One patient achieved reduction of more than 50% of involved sFLC and reduction of more than 50% of the M protein after three cycles. One patient had progressive disease. None of the responding patients with renal impairment achieved improvement of the renal function, but all responding patients showed reduction of more than 50% of initial albuminuria. After BD one patient achieved hematological CR, one VGPR and one PR (Gertz MA et al., Amyloid 2010). All responding patients were eligible for ASCT. Two patients underwent stem cell mobilization with cyclophosphamide 4 g/m2; one patient was mobilized with G-CSF alone. Melphalan dose was reduced to 140 mg/m2in the only patient undergoing hemodyalisis. There were no complications related to stem cell harvest and engraftment (only one patient showed a late platelet engraftment). After ASCT two patients achieved at least VGPR; one patient achieved a PR and he underwent second ASCT achieving again a PR. Dose reduction of Bortezomib was required in two patients because of grade 2 neuropathy. Conclusions: BD is feasible and effective in LCDD patients, and it can be used as an induction regimen before ASCT. Disclosures: Off Label Use: Bortezomib for light chain deposition disease.

scholarly journals Treatment of Light Chain Deposition Disease Using Bortezomib-Based Regimen Followed by Thalidomide-Based Regimen in a Saudi Male

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Bappa Adamu ◽  
Mushabab Al-Ghamdi ◽  
Mustafa Ahmad ◽  
Khaled O. Alsaad
Keyword(s):  
Light Chain ◽  
Light Chains ◽  
Cell Transplant ◽  
Free Light Chains ◽  
Light Chain Deposition Disease ◽  
Serum Free ◽  
Deposition Disease ◽  
Serum Free Light Chains ◽  
Light Chain Deposition ◽  
Saudi Male

Light chain deposition disease (LCDD) is a rare illness with, as yet, no clear evidence-based guidelines for its treatment. To the best of our knowledge, LCDD has not been previously reported from Saudi Arabia. We present in this report, a 38-year-old Saudi male who presented with clinical features suggestive of hypertensive nephropathy but kidney biopsy later revealed the diagnosis of LCDD. His serum creatinine at presentation was 297 μmol/L which came down to 194 μmol/L on treatment with Bortezomib, Cyclophosphamide and Dexamethasone. His 24-hour protein excretion at presentation was 6 g/L which also came down to less than 1 g/day. He was later placed on Cyclophosphamide, Thalidomide, and Dexamethasone regimen because of persistent high titres of serum free light chains. He went into remission with undetectable serum free light chains and remained so for three years at the time of writing this report. We conclude that LCDD, though rare, does occur in Saudi population. The treatment of LCDD is challenging but the use of Bortezomib, a proteosome inhibitor, is promising. However, suboptimal response may require further treatment with other therapeutic options such as chemotherapy with alkylating agents or high-dose Melphalan with autologous stem cell transplant.

scholarly journals A Phase I Trial of Pomalidomide, Bortezomib (Velcade), and Dexamethasone (PVD) As Initial Treatment of AL Amyloidosis and Light Chain Deposition Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4767-4767
Author(s):  
Jeffrey Zonder ◽  
Christiane Houde ◽  
Sascha Tuchman ◽  
Vishal Kukreti ◽  
Vaishali Sanchorawala ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Research Funding ◽  
Median Number ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Plasma Cell Dyscrasias ◽  
Light Chain Deposition

Abstract Introduction: AL amyloidosis (AL) and Light Chain Deposition Disease (LCDD) are plasma cell dyscrasias in which misfolded monoclonal light chains form insoluble extracellular protein deposits (fibrillar and amorphous, respectively). In AL particularly, toxic soluble light chain oligomers also play a role in disease pathogenesis. Treatment of AL and LCDD aims at eliminating the abnormal plasma cell clone. Typical agents used include corticosteroids, bortezomib (btz), alkylators, or immunomodulatory drugs (IMiDs) such as lenalidomide (len) or pomalidomide (pom). Len-btz-dexamethasone (dex) is a highly efficacious frontline regimen commonly used for multiple myeloma, a related plasma cell cancer. Despite this, prospective studies using btz-IMiD combos as initial therapy of AL or LCDD are lacking. Here we report our experience with pom-btz-dex(PVD) for pts with AL or LCDD. Methods: This is a prospective Phase I trial using a standard 3+3 dose escalation scheme (described in Table 1). The primary objective is to establish the maximally tolerated dosing (MTD), with assessment for dose limiting toxicity (DLT) extending through cycles 1 and 2 for each pt. Hematologic and organ responses (HR and OR) were assessed using recently updated guidelines. PVD was administered in repeating 28-day cycles until either DLT or progressive disease. Key inclusion/exclusion criteria: biopsy proven AL amyloidosis or LCDD; no more than 1 prior cycle of anti-plasma cell therapy; measurable disease defined as at least a 5 mg/dL difference between the involved (iFLC) and uninvolved (uFLC) serum free light chains, or a serum M-protein of 0.5 g/dL or greater (latter not permissible without measurable sFLCdifference after protocol amendment); ECOG PS of 2 or less; adequate renal, hepatic, and marrow function; no Grade 3 or higher peripheral neuropathy (PN; pts with painful grade 2 PN also excluded). Abnormal left ventricular ejection fraction or cardiac biomarkers allowed, but pts with NYHA class III/IV congestive heart failure or uncontrolled ventricular arrhythmias were excluded. Antithrombotic/antiviral prophylaxis was required for all pts. Results: Six pts have been enrolled thus far (3 each in cohorts 1 and 2, respectively). Three additional pts have already been identified for cohort 3. Five of 6 pts had AL, and 1 had LCDD. Median age was 65.5 yrs (range 49-74 yrs). 5 pts were female. Mayo cardiac stage I/II/III in 1, 2, and 3 pts, respectively. Three pts had one prior cycle of therapy (the others had none). The iFLC was lambda type in all 5 AL pts, and kappa for the pt with LCDD. Median number of organs involved by AL/LCDD was 2 (range, 2-4; 4 with both cardiac and renal, and 1 additional pt with cardiac). The median number of PVD cycles administered was 3 (range 1-6). Two pts are still on therapy. The reasons for stopping PVD in the other 4 pts were: sudden death due to underlying cardiac AL (during cycle 3 of PVD), pt preference after reaching maximal HR (after cycle 6), lack of HR (after cycle 3), and toxicity (after cycle 4). Baseline dex dose adjustment was required for protocol-specified reasons in all pts. One pt required further dex reduction during cycle 4 of PVD. No pts required baseline or subsequent modification of pom or btz. Table 2 summarizes reported adverse events (AEs). No DLTshave been observed. Two pts achieved HR (0 CR, 1 VGPR, 1 PR, 3 SD, 0 PD). Organ responses have not been observed, but the first protocol-specified OR assessment takes place after 4 cycles of PVD and some pts have yet to reach this time point. Conclusions: PVD was well tolerated in this group of pts with AL and LCDD. Importantly, no significant myelosuppression or PN was noted in the first 2 (out of a planned 4) dose cohorts. Most AEs have been related to the ptsÕ underlying AL/LCDD, though dex has posed difficulties for some pts. Hematologic responses have been seen, but organ responses are predictably lagging. Once the MTD is established, an 18-pt expansion cohort dosed at that level willfurther examine the efficacy of PVD as up-front treatment for AL and LCDD. Disclosures Zonder: Celgene: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. Off Label Use: Pomalidomide and Bortezomib are approved drugs for multiple myeloma; they are used in this trial as treatment for the related plasma cell dyscrasias AL amyloidosis and light chain deposition disease. . Tuchman:Celgene: Honoraria, Research Funding, Speakers Bureau; Millennium: Honoraria, Research Funding, Speakers Bureau. Kukreti:Celgene: Honoraria. Burt:Celgene: Speakers Bureau. Matous:Takeda Pharmaceuticals International Co.: Speakers Bureau; Onyx: Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Seattle Genetics, Inc.: Research Funding, Speakers Bureau.

Autologous stem cell transplant for light chain deposition disease: Incorporating bortezomib to the induction therapy

2012 ◽  
Vol 87 (8) ◽  
pp. 822-823 ◽  
Author(s):  
Victor H. Jimenez-Zepeda ◽  
Suzanne Trudel ◽  
Andrew Winter ◽  
Donna E. Reece ◽  
Christine Chen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Induction Therapy ◽  
Light Chain ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Light Chain Deposition

scholarly journals Proteinaceous (angiocentric sclerosing) lymphadenopathy: a polyclonal systemic, nonamyloid deposition disorder

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 1159-1162
Author(s):  
J Michaeli ◽  
R Niesvizky ◽  
D Siegel ◽  
M Ladanyi ◽  
PH Lieberman ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Clinical Manifestations ◽  
Response To Therapy ◽  
Plasma Cell Dyscrasia ◽  
Unknown Etiology ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Generalized Lymphadenopathy ◽  
Light Chain Deposition

Proteinaceous lymphadenopathy with hypergammaglobulinemia (PLWH) is an exceedingly rare disease of unknown etiology. Described primarily as a pathologic entity, relatively little is known about its clinical manifestations or its response to therapy. The disease is often referred to and treated as an unusual form of plasma cell dyscrasia or light chain deposition disease. We have recently encountered a young patient with PLWH who presented with generalized lymphadenopathy, marked liver function abnormalities, hypocomplementemia, cryoglobulinemia, decreased T4/T8 ratio, and ophthalmopathy. Contrary to the notion that PLWH is a clonal disorder, we found no evidence of clonality in this patient. The most characteristic finding in this and in another patient, previously seen at our institution, was marked angiocentric hyaline sclerosis of the small and mid-sized blood vessels of involved lymph nodes and organs. Based on these findings, we propose the term angiocentric sclerosing lymphadenopathy, which more accurately defines this clinicopathologic entity that appears to be distinct from light chain deposition disease and other plasma cell dyscrasias.

scholarly journals Proteinaceous (angiocentric sclerosing) lymphadenopathy: a polyclonal systemic, nonamyloid deposition disorder

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 1159-1162 ◽  
Author(s):  
J Michaeli ◽  
R Niesvizky ◽  
D Siegel ◽  
M Ladanyi ◽  
PH Lieberman ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Clinical Manifestations ◽  
Response To Therapy ◽  
Plasma Cell Dyscrasia ◽  
Unknown Etiology ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Generalized Lymphadenopathy ◽  
Light Chain Deposition

Abstract Proteinaceous lymphadenopathy with hypergammaglobulinemia (PLWH) is an exceedingly rare disease of unknown etiology. Described primarily as a pathologic entity, relatively little is known about its clinical manifestations or its response to therapy. The disease is often referred to and treated as an unusual form of plasma cell dyscrasia or light chain deposition disease. We have recently encountered a young patient with PLWH who presented with generalized lymphadenopathy, marked liver function abnormalities, hypocomplementemia, cryoglobulinemia, decreased T4/T8 ratio, and ophthalmopathy. Contrary to the notion that PLWH is a clonal disorder, we found no evidence of clonality in this patient. The most characteristic finding in this and in another patient, previously seen at our institution, was marked angiocentric hyaline sclerosis of the small and mid-sized blood vessels of involved lymph nodes and organs. Based on these findings, we propose the term angiocentric sclerosing lymphadenopathy, which more accurately defines this clinicopathologic entity that appears to be distinct from light chain deposition disease and other plasma cell dyscrasias.

scholarly journals Pulmonary light chain deposition disease: a case series and literature review

2020 ◽  
Vol 8 (9) ◽  
pp. 588-588
Author(s):  
Ping Wei ◽  
Rujia Tao ◽  
Yihan Liu ◽  
Huikang Xie ◽  
Sen Jiang ◽  
...  
Keyword(s):  
Literature Review ◽  
Light Chain ◽  
Case Series ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Light Chain Deposition

Outcomes of autologous stem cell transplant for cardiac AL-amyloidosis and cardiac light chain deposition disease

2019 ◽  
Vol 26 (5) ◽  
pp. 1128-1133
Author(s):  
Al-Ola A Abdallah ◽  
Daisy Alapat ◽  
Varinder Kaur ◽  
Shebli Atrash
Keyword(s):  
Stem Cell ◽  
Light Chain ◽  
Cardiac Amyloidosis ◽  
Stem Cell Transplant ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Light Chain Deposition

Introduction Cardiac amyloidosis and light chain deposition disease (LCDD) are the most common cause of death in AL amyloidosis or LCDD. Methods Our multiple myeloma database identified 50 patients with cardiac amyloidosis or LCDD between January 2004 and January 2013. Descriptive analyses were performed on available data for patient characteristics, disease course, and outcomes. Results The median age at diagnosis was 61 years for those who received autologous hematopoietic stem cell transplant (ASCT) and 71 years for those who received only bortezomib-based chemotherapy; 62.5% (n = 30) of patients had elevated levels of NT-proBNP ≥323 ng/L, and 29.2% (n = 14) of patients had an elevated cTnT ≥0.1 µg/L. Echocardiogram findings showed a speckled appearance in 18% (n = 9) of patients, and 60% (n = 30) of patients had an increased diastolic intra-ventricular septum (IVSD) thickness measuring ≥1.3 cm; 64.3% (n = 18) of patients who underwent cardiac MRI showed subendocardial enhancement. Out of 48 patients who received treatment, 37 patients were diagnosed with cardiac amyloidosis and 11 patients were diagnosed with cardiac LCDD. Twenty-eight patients (75.7%) with cardiac amyloidosis received ASCT, compared to 34.3% (n = 9) patients who were ineligible for ASCT and received chemotherapy only. Patients who underwent ASCT had a median OS of 4.48 years compared to 1.82 years (p = 0.69) for those receiving chemotherapy alone. Conclusion Our single institution experience shows that ASCT is feasible for cardiac amyloidosis and/or cardiac LCDD. However, careful selection of proper patients and diligent supportive care are vital to decreasing transplant-related mortality.

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