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Article ; Online: Immunoglobulin Light Chain Amyloidosis: Diagnosis and Risk Assessment.

Zanwar, Saurabh / Gertz, Morie A / Muchtar, Eli

Journal of the National Comprehensive Cancer Network : JNCCN

2023 Volume 21, Issue 1, Page(s) 83–90

Abstract: Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder with multiple clinical presentations. The diagnosis of AL amyloidosis requires a high index of suspicion, making a delay in diagnosis common, which contributes to the high early ...

Abstract	Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder with multiple clinical presentations. The diagnosis of AL amyloidosis requires a high index of suspicion, making a delay in diagnosis common, which contributes to the high early mortality seen in this disease. Establishing the diagnosis of AL amyloidosis requires the demonstration of tissue deposition of amyloid fibrils. A bone marrow biopsy and fat pad aspirate performed concurrently have a high sensitivity for the diagnosis of AL amyloidosis and negate the need for organ biopsies in most patients. An accurate diagnosis requires amyloid typing via additional testing, including tissue mass spectrometry. Prognostication for AL amyloidosis is largely driven by the organs impacted. Cardiac involvement represents the single most important prognostic marker, and the existing staging systems are driven by cardiac biomarkers. Apart from organ involvement, plasma cell percentage on the bone marrow biopsy, specific fluorescence in situ hybridization findings, age at diagnosis, and performance status are important prognostic markers. This review elaborates on the diagnostic testing and prognostication for patients with newly diagnosed AL amyloidosis.
MeSH term(s)	Humans ; Immunoglobulin Light-chain Amyloidosis/diagnosis ; Amyloidosis/diagnosis ; Amyloidosis/pathology ; In Situ Hybridization, Fluorescence ; Plasma Cells/pathology ; Risk Assessment
Language	English
Publishing date	2023-01-01
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2250759-0
ISSN	1540-1413 ; 1540-1405
ISSN (online)	1540-1413
ISSN	1540-1405
DOI	10.6004/jnccn.2022.7077
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Article: Early intervention in asymptomatic chronic lymphocytic leukemia.

Muchtar, Eli / Kay, Neil E / Parikh, Sameer A

Clinical advances in hematology & oncology : H&O

2021 Volume 19, Issue 2, Page(s) 92–103

Abstract: Of the estimated 21,000 patients who will receive a new diagnosis of chronic lymphocytic leukemia (CLL) this year in the United States, approximately 80% will have early-stage disease. Patients with early-stage disease do not meet the criteria in the ... ...

Abstract	Of the estimated 21,000 patients who will receive a new diagnosis of chronic lymphocytic leukemia (CLL) this year in the United States, approximately 80% will have early-stage disease. Patients with early-stage disease do not meet the criteria in the 2018 International Workshop on CLL guidelines for the initiation of therapy, and therefore they are not routinely offered treatment. The current management of these patients follows a "watch-and-wait" paradigm, which entails a regular follow-up every 3 to 6 months that includes a physical examination and relevant laboratory testing to evaluate for disease progression. These recommendations are based on decades of careful observations showing that treatment in early-stage CLL does not improve overall survival. With the advent of better prognostic tools to identify patients at high risk, in addition to the recent approval of several novel oral agents with impressive efficacy, the time is ripe to re-examine this question. This review (1) summarizes the results of studies of early intervention in CLL that led to the current consensus for "watch and wait" in early-stage CLL, (2) discusses the role of contemporary risk stratification in early-stage CLL, (3) describes the adverse clinical complications of untreated CLL, and (4) presents the results of ongoing clinical trials of novel agents used in patients with early-stage CLL.
MeSH term(s)	Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asymptomatic Diseases ; Biomarkers ; Clinical Trials as Topic ; Disease Progression ; Drugs, Investigational/therapeutic use ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Male ; Multicenter Studies as Topic ; Neoplasm Staging ; Practice Guidelines as Topic ; Prognosis ; Quality of Life ; Risk Assessment ; Watchful Waiting
Chemical Substances	Antineoplastic Agents ; Biomarkers ; Drugs, Investigational
Language	English
Publishing date	2021-03-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2271951-9
ISSN	1543-0790
ISSN	1543-0790
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Article ; Online: The colorful landscape of multiple myeloma.

Muchtar, Eli / Gertz, Morie A

Leukemia & lymphoma

2019 Volume 60, Issue 9, Page(s) 2099–2100

MeSH term(s)	Bortezomib ; Humans ; Multiple Myeloma ; Prognosis ; Sialic Acid Binding Ig-like Lectin 3
Chemical Substances	CD33 protein, human ; Sialic Acid Binding Ig-like Lectin 3 ; Bortezomib (69G8BD63PP)
Language	English
Publishing date	2019-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2019.1585842
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Zs.A 2997: Show issues

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Article ; Online: Monitoring Tafamidis, The Most Expensive Cardiac Medication: Are Serum Transthyretin Levels the Answer?

Chang, Ian C / Muchtar, Eli / Grogan, Martha

JACC. CardioOncology

2021 Volume 3, Issue 4, Page(s) 587–589

Language	English
Publishing date	2021-10-19
Publishing country	United States
Document type	Editorial
ISSN	2666-0873
ISSN (online)	2666-0873
DOI	10.1016/j.jaccao.2021.09.007
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Article ; Online: 67-Year-Old Man With Fatigue, Lightheadedness, and Erythrocytosis.

Stewart, Glenn A / Smith, Caleb J / Muchtar, Eli

Mayo Clinic proceedings

2021 Volume 96, Issue 7, Page(s) 1949–1954

MeSH term(s)	Aged ; Carcinoma, Renal Cell/pathology ; Carcinoma, Renal Cell/physiopathology ; Carcinoma, Renal Cell/surgery ; Diagnosis, Differential ; Dizziness/diagnosis ; Erythropoietin/analysis ; Erythropoietin/biosynthesis ; Fatigue/diagnosis ; Fatigue/etiology ; Humans ; Kidney Neoplasms/pathology ; Kidney Neoplasms/physiopathology ; Kidney Neoplasms/surgery ; Lung Neoplasms/diagnostic imaging ; Lung Neoplasms/secondary ; Male ; Nephrectomy/methods ; Polycythemia/diagnosis ; Polycythemia/etiology ; Tomography, X-Ray Computed/methods ; Treatment Outcome
Chemical Substances	Erythropoietin (11096-26-7)
Language	English
Publishing date	2021-07-04
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	124027-4
ISSN	1942-5546 ; 0025-6196
ISSN (online)	1942-5546
ISSN	0025-6196
DOI	10.1016/j.mayocp.2020.11.036
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Article ; Online: Updates in the Diagnosis and Management of AL Amyloidosis.

Cook, Joselle / Muchtar, Eli / Warsame, Rahma

Current hematologic malignancy reports

2020 Volume 15, Issue 3, Page(s) 155–167

Abstract: Purpose of review: Light chain (AL) amyloidosis is an insidious progressive disease which results in significant morbidity and inevitable mortality if not diagnosed and treated promptly. This review will highlight recent developments and summarize ... ...

Abstract	Purpose of review: Light chain (AL) amyloidosis is an insidious progressive disease which results in significant morbidity and inevitable mortality if not diagnosed and treated promptly. This review will highlight recent developments and summarize critical clinical points and updated practice changes for the clinician in 2020. Recent findings: Comparative analyses of staging systems, updated prognostic tools, and treatment response criteria now allow for improved patient stratification and treatment decisions; the role of minimal residual disease in response assessment is still being assessed. Clinical and genetic predictors for long-term survivors have been highlighted. Standard-of-care front-line bortezomib and the integration of anti-CD38 monoclonal antibodies in the relapsed disease have transformed treatment approach in recent years. Various clinical trials in the pipeline include novel anti-plasma cell therapies and therapies directed against amyloid deposits which promise to further advance the treatment landscape. Diagnosis, response assessment, and treatment paradigms for AL amyloidosis have evolved significantly in the past 15 years, translating into superior outcomes and increased chances of long-term survival for AL amyloidosis.
MeSH term(s)	ADP-ribosyl Cyclase 1/antagonists & inhibitors ; ADP-ribosyl Cyclase 1/immunology ; Animals ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/therapeutic use ; Bortezomib/adverse effects ; Bortezomib/therapeutic use ; Clinical Decision-Making ; Humans ; Immunoglobulin Light-chain Amyloidosis/diagnosis ; Immunoglobulin Light-chain Amyloidosis/genetics ; Immunoglobulin Light-chain Amyloidosis/immunology ; Immunoglobulin Light-chain Amyloidosis/therapy ; Immunologic Factors/adverse effects ; Immunologic Factors/therapeutic use ; Membrane Glycoproteins/antagonists & inhibitors ; Membrane Glycoproteins/immunology ; Predictive Value of Tests ; Proteasome Inhibitors/adverse effects ; Proteasome Inhibitors/therapeutic use ; Risk Factors ; Stem Cell Transplantation/adverse effects ; Treatment Outcome
Chemical Substances	Antibodies, Monoclonal ; Immunologic Factors ; Membrane Glycoproteins ; Proteasome Inhibitors ; Bortezomib (69G8BD63PP) ; CD38 protein, human (EC 3.2.2.5) ; ADP-ribosyl Cyclase 1 (EC 3.2.2.6)
Language	English
Publishing date	2020-05-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2229765-0
ISSN	1558-822X ; 1558-8211
ISSN (online)	1558-822X
ISSN	1558-8211
DOI	10.1007/s11899-020-00574-5
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Zs.A 6332: Show issues

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Article: Clinical trials evaluating potential therapies for light chain (AL) amyloidosis.

Muchtar, Eli / Gertz, Morie A

Expert opinion on orphan drugs

2017 Volume 5, Issue 8, Page(s) 655–663

Abstract: Introduction: The field of systemic amyloidosis is experiencing major advances in diagnostic and prognostic methods coupled with a growing availability in treatment options.: Areas covered: Treatment of AL amyloidosis traditionally targeted the ... ...

Abstract	Introduction: The field of systemic amyloidosis is experiencing major advances in diagnostic and prognostic methods coupled with a growing availability in treatment options. Areas covered: Treatment of AL amyloidosis traditionally targeted the clonal plasma cells, in order to block further production of amyloidogenic light chains. Currently, a research focus is placed on targeting the already formed amyloid deposits using monoclonal antibodies against epitopes on such deposits. Encouraging results were obtained from the three investigated antibodies: NEOD001, 11-1F4 and anti-SAP, but further validation is required before these antibodies can be commercialized. In this paper, we review the current active clinical research in AL amyloidosis, which includes the monoclonal antibodies targeting amyloid deposits, daratumumab, Venetoclax, doxycycline, green tea, pomalidomide, carfilzomib and ixazomib. Expert opinion: Monoclonal antibodies, targeting either the amyloid deposits or the plasma cell compartment will likely be integrated into routine treatment practice given their encouraging results and minimal toxicity in the fragile population of AL amyloidosis. Other therapeutic options hold promise to the field as well, but toxicity will likely challenge their routine use. Early recognition remains the best option for outcome enhancement.
Language	English
Publishing date	2017-04-27
Publishing country	England
Document type	Journal Article
ISSN	2167-8707
ISSN	2167-8707
DOI	10.1080/21678707.2017.1341834
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Article ; Online: The Challenges in Chemotherapy and Stem Cell Transplantation for Light-Chain Amyloidosis.

Muchtar, Eli / Lin, Grace / Grogan, Martha

The Canadian journal of cardiology

2019 Volume 36, Issue 3, Page(s) 384–395

Abstract: Light-chain (AL) amyloidosis is a systemic syndrome characterized by progressive organ dysfunction leading to organ failure and death. The heart is the most commonly involved organ and the leading determinant of short- and long-term survival. Pathogenic ... ...

Abstract	Light-chain (AL) amyloidosis is a systemic syndrome characterized by progressive organ dysfunction leading to organ failure and death. The heart is the most commonly involved organ and the leading determinant of short- and long-term survival. Pathogenic free light chains, fragments of intact immunoglobulins, are the amyloidogenic proteins and are secreted by clonal bone marrow plasma cells. The goal of therapy is to cut off the supply of these light chains to allow organ recovery. Therapies for AL amyloidosis are based on therapies used to treat multiple myeloma, which is a more common plasma cell disorder. However, because patients with AL amyloidosis have organ dysfunction, including multiorgan involvement, they generally have poor treatment tolerance and increased treatment toxicity. Unfortunately, the consequences of toxicity and difficulty in tolerating treatment may result in a fatal outcome. Therefore, treatment should balance the goal of achieving a rapid and meaningful reduction in the circulating light chains while maximizing patient safety. This approach is best achieved by a multidisciplinary approach involving related medical disciplines. This review describes the challenges of managing patients with AL amyloidosis and provides a guide for physicians with a specific focus on cardiac management. We address the role of autologous stem cell transplantation vs standard-intensity therapies in a risk-adapted approach and discuss the management of commonly encountered toxicities. Guidance on response assessment, including organ response, is provided. With expansion in treatment options, we anticipate continuous improvement in outcome for this disease. Nonetheless, early diagnosis remains the best approach to improve disease burden and outcome.
MeSH term(s)	Cardiomyopathies/drug therapy ; Cardiomyopathies/surgery ; Decision Trees ; Humans ; Immunoglobulin Light-chain Amyloidosis/drug therapy ; Immunoglobulin Light-chain Amyloidosis/surgery ; Stem Cell Transplantation
Language	English
Publishing date	2019-12-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	632813-1
ISSN	1916-7075 ; 0828-282X
ISSN (online)	1916-7075
ISSN	0828-282X
DOI	10.1016/j.cjca.2019.11.032
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Zs.A 2150: Show issues

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Article ; Online: New developments in diagnosis, risk assessment and management in systemic amyloidosis.

Vaxman, Iuliana / Dispenzieri, Angela / Muchtar, Eli / Gertz, Morie

Blood reviews

2019 Volume 40, Page(s) 100636

Abstract: Amyloidosis is a group of disorders characterized by a misfolded protein that deposits in organs and compromise their function. Clinician should have a high index of suspicion because in most cases, the clinical picture is non-specific. Typing of amyloid ...

Abstract	Amyloidosis is a group of disorders characterized by a misfolded protein that deposits in organs and compromise their function. Clinician should have a high index of suspicion because in most cases, the clinical picture is non-specific. Typing of amyloid is of utmost importance and should be an integral part of accurately diagnosing a patient. AL amyloidosis is the most common systemic amyloidosis in the western world in which the misfolded proteins are immunoglobulin light chains secreted by clonal plasma cells. New data about prognostication of AL amyloidosis patients are accumulating. The treatment goal is to eradicate the amyloidogenic plasma cell clone, by using high dose melphalan and/or novel agents (proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies against CD38). Early diagnosis is important for effectively treating the patient as late diagnosis hampers chances for organ recovery. ATTR amyloidosis is less recognized but is increasingly seen due to better recognition and improved diagnostic tools. New data about treatment options (patisiran, inotersen and tafamidis) have recently been published and are discussed.
MeSH term(s)	Humans ; Immunoglobulin Light Chains/metabolism ; Immunoglobulin Light-chain Amyloidosis/diagnosis ; Immunoglobulin Light-chain Amyloidosis/drug therapy ; Immunoglobulin Light-chain Amyloidosis/metabolism ; Immunoglobulin Light-chain Amyloidosis/pathology ; Plasma Cells/metabolism ; Plasma Cells/pathology ; Risk Assessment
Chemical Substances	Immunoglobulin Light Chains
Language	English
Publishing date	2019-11-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	639015-8
ISSN	1532-1681 ; 0268-960X
ISSN (online)	1532-1681
ISSN	0268-960X
DOI	10.1016/j.blre.2019.100636
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Zs.A 2207: Show issues

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Article: Elotuzumab: the first approved monoclonal antibody for multiple myeloma treatment.

Magen, Hila / Muchtar, Eli

Therapeutic advances in hematology

2016 Volume 7, Issue 4, Page(s) 187–195

Abstract: Elotuzumab is a monoclonal antibody directed against the SLAMF7 receptor, expressed on normal and malignant plasma cells with a lower expression on other lymphoid cells such as natural killer (NK) cells. Elotuzumab has no significant antimyeloma activity ...

Abstract	Elotuzumab is a monoclonal antibody directed against the SLAMF7 receptor, expressed on normal and malignant plasma cells with a lower expression on other lymphoid cells such as natural killer (NK) cells. Elotuzumab has no significant antimyeloma activity when given as a single agent to patients with relapsed or refractory multiple myeloma (RRMM). However, when combined with other antimyeloma agents, it results in improved response and outcome. Owing to the results from the landmark ELOQUENT-2 phase III clinical trial, which compared lenalidomide and dexamethasone with or without elotuzumab in patients with RRMM, elotuzumab in combination with lenalidomide and dexamethasone was approved by the American Food and Drug Administration (FDA) in November 2015 for multiple myeloma (MM) patients who received one to three prior lines of therapy. This review will give a brief description of the signaling lymphocytic activation molecule (SLAM) family receptors, the unique SLAMF7 receptor and the mechanism of action of elotuzumab. Thereafter, we will give an overview on its antimyeloma activity in preclinical and clinical trials, including its toxicity profile and management thereof.
Language	English
Publishing date	2016-06-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2585183-4
ISSN	2040-6215 ; 2040-6207
ISSN (online)	2040-6215
ISSN	2040-6207
DOI	10.1177/2040620716652862
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