AL Amyloidosis

Table of Contents

  1. What is AL Amyloidosis?
  2. How Amyloid Fibrils Form
  3. The Heart: The Organ That Drives Prognosis
  4. Kidney Involvement: Nephrotic Syndrome
  5. Neurological Manifestations
  6. Recognizing AL Amyloidosis: The Visible Signs
  7. Diagnosis: Tissue Biopsy and Congo Red Stain
  8. Staging: Mayo 2004 and Mayo 2012 Systems
  9. Treatment: Eliminating the Plasma Cell Clone
  10. Organ Recovery and Long-Term Outcomes
  11. Liver and Gastrointestinal Involvement
  12. Key Research Papers
  13. Connections
  14. Featured Videos

What is AL Amyloidosis?

AL amyloidosis — immunoglobulin light chain amyloidosis, called primary systemic amyloidosis in older papers — is described in the 2024 Gertz review as a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light (or, rarely, heavy) chains are deposited in tissues. A clone of plasma cells makes a light chain that misfolds, and the 2023 Zanwar review describes the deposits as insoluble beta-pleated sheets of misfolded light chains. The 2018 Merlini review calls it a progressive protein misfolding disease in which light chains convert from their soluble, functional state into highly organized amyloid fibrils that cause organ dysfunction, with cardiac and kidney damage predominating.

The Zanwar review describes AL as the most frequently encountered systemic amyloidosis, yet uncommon, with an estimated incidence of about 1 patient per 100,000 person-years, or 3,500 to 4,500 new patients a year in the United States. A US claims study (Quock 2018) found an incidence of 9.7 to 14.0 cases per million person-years between 2007 and 2015, with no significant change over that time, while prevalence rose from 15.5 to 40.5 cases per million. The 2020 Gertz–Dispenzieri systematic review gives an incidence of about 12 cases per million persons per year.

AL amyloidosis is related to multiple myeloma: both arise from a plasma cell clone. In a Mayo Clinic series of 1,255 AL patients (Kourelis 2013), 8% also met the CRAB criteria for myeloma (high calcium, kidney failure, anemia, lytic bone lesions), 38% had more than 10% bone marrow plasma cells without CRAB features, and 54% had 10% or fewer; median overall survival was 10.6, 16.2 and 46 months respectively, and the authors proposed that more than 10% marrow plasma cells be treated as AL amyloidosis with myeloma. The Zanwar review gives about 10% as the average marrow plasma cell involvement in AL.

In 730 newly diagnosed patients (Kumar 2010), the plasma cell clone made lambda light chains in 72% and kappa in 28%. Kappa disease involved the gut and liver more often and lambda disease the kidney; overall survival was similar for the two.

Survival without treatment is short. The 2021 ESC position statement lists a median survival from diagnosis of 24 months for AL amyloidosis, and 6 months when heart failure is present at diagnosis and untreated. The Gertz–Dispenzieri review reports that 25% of AL patients die within 6 months of diagnosis, and the Zanwar review that, despite falling early mortality, up to 30% die within 6 months, mostly from cardiac amyloidosis. The 2024 Gertz review names delayed diagnosis as a major obstacle to starting effective therapy before end-stage organ failure.

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How Amyloid Fibrils Form

More than 30 different proteins can form amyloid fibrils in humans (Zanwar 2023; ESC 2021), and the ESC statement notes that only nine of them accumulate in the heart enough to cause significant cardiac disease. In AL amyloidosis the precursor is the free light chain made by the plasma cell clone (Kumar 2010).

Light Chain Genes and Organ Pattern

Which organs are hit depends partly on the light chain itself. In a study that sequenced the light-chain variable genes of 60 AL patients (Comenzo 2001), clones from the lambda VI (6a) germline gene were more likely to present with dominant kidney involvement, clones from the 1c, 2a2 and 3r lambda genes with dominant heart and multisystem disease, and kappa clones with dominant liver involvement. In the same study's laboratory model, lambda VI light chains formed amyloid rapidly, unlike the other AL light chains tested. Patients who met myeloma criteria were more likely to have dominant heart involvement regardless of gene use.

Serum Amyloid P Component

Serum amyloid P component (SAP), a normal plasma protein, binds to the fibrils in all types of amyloid deposits and contributes to the disease (Pepys 2002). Its binding is used for imaging: in a 1990 study, iodine-123-labelled SAP localized rapidly and specifically in amyloid deposits and appeared to show the extent of deposition in all 50 patients with systemic amyloidosis, with no uptake in controls; uptake in the heart, skin, carpal region and bone marrow was seen only in the AL type (Hawkins 1990). In metabolic studies, labelled SAP persisted in amyloid deposits with a half-time of 24 days, and the authors concluded that plasma SAP is in dynamic equilibrium with a very large amyloid pool (Hawkins, Wootton and Pepys 1990).

The Merlini review describes passive immunotherapies that directly accelerate removal of amyloid deposits as a promising direction, and the 2024 Gertz review notes that trials of antibodies to deplete deposited fibrils are underway.

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The Heart: The Organ That Drives Prognosis

The ESC statement gives heart involvement in about 70% of AL patients. The Zanwar review describes the heart as the most commonly involved organ and cardiac involvement as the single most important prognostic marker, with much of the early mortality driven by it. AL amyloidosis can present as heart failure with preserved ejection fraction (Gertz 2024); cardiac amyloidosis has its own page.

ECG and Echocardiogram

The Zanwar review describes the classic combination of concentric cardiac thickening, an increased interventricular septal thickness and a normal-to-low voltage electrocardiogram, but notes that multiple confounders limit the sensitivity of these findings. The thickening tends to involve both ventricles, unlike high blood pressure, where it is commonly left-sided, and a strain pattern with a base-to-apex gradient is a more specific echocardiographic abnormality. Ventricular arrhythmias and electromechanical dissociation are described as a common cause of cardiac death, especially sudden cardiac death.

The ESC statement's echocardiographic criteria start from unexplained left ventricular wall thickness of 12 mm or more plus at least two of: grade 2 or worse diastolic dysfunction; tissue Doppler s′, e′ and a′ velocities below 5 cm/s; and reduced global longitudinal strain. Its other echo red flags:

On the ECG, the ESC statement lists low QRS voltage for the degree of wall thickness and a pseudoinfarct pattern as red flags.

Cardiac Biomarkers

NT-proBNP (N-terminal pro-B-type natriuretic peptide) and cardiac troponin are the basis of the Mayo staging systems (Dispenzieri 2004; Kumar 2012; see Staging below). In 816 patients from seven referral centres, changes in NT-proBNP after therapy reliably reflected changes in cardiac function, and changes in free light chains and NT-proBNP predicted survival as early as 3 months after treatment began (Palladini 2012).

Heart Failure Medicines: What Studies Report

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Kidney Involvement: Nephrotic Syndrome

The kidney is involved in 70% of AL patients according to Palladini 2014, and in 50% to 70% according to the Zanwar review, which lists the heart and kidneys as the most commonly involved organs. The Gertz 2024 review lists nephrotic syndrome among the presenting features, and the Gertz–Dispenzieri review places amyloidosis in the differential diagnosis of nephrotic syndrome in adults without diabetes. The Zanwar review notes that non-selective proteinuria above 0.5 g/24 hours, together with amyloid shown outside the kidney, removes the need for a kidney biopsy.

Renal Staging

In 461 patients from Pavia, validated in 271 from Heidelberg, proteinuria above 5 g/24 hours and an estimated glomerular filtration rate (eGFR) below 50 mL/min best predicted progression to dialysis (Palladini 2014). As tabulated in the Zanwar review, the 3-year risk of dialysis in the testing and validation cohorts was:

Renal Response and Outcome

In the same study, a fall in eGFR of 25% or more at 6 months predicted poor renal survival and was adopted as the criterion for renal progression; a fall in proteinuria of at least 30%, or to below 0.5 g/24 hours, without renal progression was the criterion for renal response. A very good partial or complete hematologic response at 6 months improved renal outcome in both cohorts. The Zanwar review notes that when the heart and kidneys are both involved, survival is largely set by the heart and most patients die before end-stage kidney disease, while kidney-only disease has a favourable outcome, with an 8-year overall survival of 80%.

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Neurological Manifestations

The Zanwar review lists the nerves as the next most commonly involved organ after the heart and kidneys.

Peripheral Neuropathy

The Zanwar review describes patients with a symmetric, distal, painful peripheral neuropathy, with or without an autonomic component, who often have an extensive neurologic evaluation before AL amyloidosis is diagnosed; in one study of neuropathy as the first manifestation, the median delay from symptom onset to diagnosis was 21 months. The review notes other causes of neuropathy associated with a monoclonal protein (cryoglobulinemia, POEMS syndrome, IgM neuropathy) and common neuropathies in which a monoclonal protein is incidental (chronic inflammatory demyelinating polyneuropathy). The Gertz–Dispenzieri review describes the neuropathy as distal sensory, with numbness, paresthesia and dysesthesias, and notes that autonomic symptoms are occasionally the presenting feature.

Autonomic Neuropathy

Dysautonomia and polyneuropathy are on the ESC list of red flags for AL amyloidosis. The Zanwar review lists autonomic involvement among prognostic factors, and the Mahmood 2014 review describes midodrine for postural (orthostatic) hypotension and thigh-high compression stockings as part of supportive care.

Carpal Tunnel Syndrome

Bilateral carpal tunnel syndrome is among the classic findings that may trigger an evaluation for systemic amyloidosis, though the Zanwar review describes these findings as uncommon. In the 1990 SAP scintigraphy study, uptake in the carpal region was seen only in AL patients (Hawkins 1990).

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Recognizing AL Amyloidosis: The Visible Signs

The Zanwar review lists macroglossia (an enlarged tongue), bilateral carpal tunnel syndrome and periorbital ecchymoses (“raccoon eyes”, bruising around the eyes) as classic clinical findings that may trigger an evaluation for systemic amyloidosis, but describes them as uncommon. The ESC statement lists macroglossia and skin bruising as red flags pointing to the AL type.

The same review describes other, nonspecific presentations that need a high index of suspicion: joint pain or arthritis and muscle disease, hormone problems (hypothyroidism, hypogonadism) and bleeding tendency. For bleeding, it describes screening with the prothrombin time and partial thromboplastin time and measuring factor X, and ruling out acquired von Willebrand disease when those are normal.

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Diagnosis: Tissue Biopsy and Congo Red Stain

The diagnosis has two parts: showing amyloid in tissue, and showing that the amyloid is made of immunoglobulin light chains rather than another protein (Gertz 2024; Zanwar 2023).

Finding the Monoclonal Protein

The Zanwar review describes establishing a monoclonal protein as the first step, because its absence makes AL amyloidosis extremely unlikely: in a Mayo Clinic study, only 1 of 522 evaluable patients (0.2%) had AL amyloidosis with normal results on all monoclonal protein studies. The full evaluation it describes is serum electrophoresis and immunofixation, a 24-hour urine collection for electrophoresis and immunofixation, and the serum free light chain assay. The ESC statement reports that serum and urine immunofixation plus serum free light chain measurement together have 99% sensitivity for the abnormal precursor in AL amyloidosis.

The difference between the involved and uninvolved free light chains (dFLC) is used for staging and for measuring response (Kumar 2012; Palladini 2012).

Tissue Biopsy and Congo Red Staining

A tissue biopsy stained with Congo red showing amyloid deposits with apple-green birefringence under polarized light is required for the diagnosis (Gertz 2024). The Zanwar review notes that thioflavin T or sulfated alcian blue can be used in place of Congo red.

Biopsy Site Selection

Sensitivities reported in the Zanwar review:

The 2024 Gertz review reports that a biopsy of the affected organ itself is not required in 85% of patients. About 10% to 20% of patients have a negative fat pad and bone marrow; when suspicion stays high, the Zanwar review describes biopsy of the suspected organ, with attention to specimen adequacy. Amyloid found incidentally in marrow or fat without a clinical syndrome had a low risk (2.7%) of progressing to systemic disease with organ involvement.

Amyloid Typing: The Critical Second Step

The 2024 Gertz review describes verifying that the amyloid is made of immunoglobulin light chains as mandatory, with laser capture mass spectrometry as the gold standard. The Zanwar review explains that typing matters even when a monoclonal protein is present, because a monoclonal gammopathy can be unrelated to the amyloid. Mass spectrometry types all forms with one test and a small amount of tissue; immunohistochemistry, immunofluorescence and immunogold electron microscopy are described as less accurate because antibodies exist only for common types. In a study of 320 Congo red–positive specimens that immunohistochemistry had not typed, mass spectrometry identified the amyloid protein in 255 (80%). The ESC statement likewise names mass spectrometry as the gold standard, with immunohistochemistry or immunoelectron microscopy used routinely.

The main type to separate from AL is transthyretin (ATTR) amyloidosis. The Zanwar review notes that the technetium-99m pyrophosphate (PYP) scan used to diagnose ATTR cardiac amyloidosis can also be positive in AL cardiac amyloidosis, so when a monoclonal protein is present the scan cannot settle the type and tissue typing is pursued.

Cardiac MRI

Characteristic cardiac magnetic resonance findings in the ESC statement are diffuse subendocardial or transmural late gadolinium enhancement (LGE) and an extracellular volume of 0.40 or more. The Zanwar review attributes LGE to the expanding interstitial amyloid and links transmural LGE to advanced cardiac involvement.

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Staging: Mayo 2004 and Mayo 2012 Systems

The Zanwar review describes the commonly used staging systems as driven by cardiac biomarkers, because cardiac involvement is the main determinant of outcome.

Mayo 2004 Staging System

The original system was built from 242 newly diagnosed Mayo Clinic patients and uses NT-proBNP with cardiac troponin T (or troponin I): both low is stage I, one high is stage II, both high is stage III (Dispenzieri 2004). The thresholds tabulated in the Zanwar review are NT-proBNP of 332 ng/L or more and troponin T of 0.035 μg/L or more; a BNP of 81 ng/L was established as the closest match to the NT-proBNP cut-off.

Those are the troponin T model's figures; the troponin I model gave 27.2, 11.1 and 4.1 months (Dispenzieri 2004).

Mayo 2012 Revised Staging System

The revised system, developed in 810 newly diagnosed patients and validated in two other datasets, adds the free light chain difference. One point each for dFLC of 18 mg/dL or more, troponin T of 0.025 ng/mL or more and NT-proBNP of 1,800 pg/mL or more gives stages I to IV (Kumar 2012):

The 2024 Gertz review gives 5-year survivals of 82%, 62%, 34% and 20% across the four stages. The Zanwar review notes that high-sensitivity troponin T is now the cardiac biomarker of choice and that conversion tables exist for the older assay.

European Modification

The European modification splits Mayo 2004 stage III by NT-proBNP: above 8,500 ng/L is stage IIIb (Zanwar 2023). In 346 stage III patients from the United Kingdom, Italy, Germany and Greece, median overall survival was 7 months and 42% died before the first response evaluation; NT-proBNP above 8,500 ng/L and systolic blood pressure below 100 mm Hg independently identified a group with a median survival of only 3 months (Wechalekar 2013). The FDA labeling for subcutaneous daratumumab states that it is not indicated, and not recommended outside controlled trials, for AL patients with NYHA class IIIB or IV heart disease or Mayo stage IIIB.

A separate renal staging system predicts the risk of dialysis (Palladini 2014; see Kidney Involvement above).

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Treatment: Eliminating the Plasma Cell Clone

Treatment is aimed at the plasma cell clone that makes the amyloid-forming light chain. The 2024 Gertz review states that all patients with a systemic amyloid syndrome require therapy to prevent amyloid deposition in other organs and progressive organ failure, and gives a very good partial response or better as the goal. In the Palladini 2012 analysis, the extent of the fall in amyloid-forming free light chains correlated strongly with improved survival.

What follows reports trial results, reviews and FDA labeling; decisions about treatment belong with a clinician.

Hematologic Response Definitions

Validated in 816 patients and a separate cohort of 374 (Palladini 2012):

The Zanwar review reports that complete response plus VGPR can be reached with first-line therapy in about 65% to 80% of patients; that patients with a baseline dFLC below 50 mg/L are not evaluable by these criteria, and a fall to below 10 mg/L (a “low-dFLC partial response”) carries prognostic value for them; and that organ response is typically delayed, coming 6 to 12 months after therapy starts.

Daratumumab + CyBorD: The Current First-Line Combination

The phase 3 ANDROMEDA trial (Kastritis 2021, N Engl J Med) randomly assigned 388 newly diagnosed patients to six cycles of bortezomib, cyclophosphamide and dexamethasone (CyBorD) alone or with subcutaneous daratumumab, followed by daratumumab every 4 weeks for up to 24 cycles. At a median follow-up of 11.4 months:

On January 15, 2021, the FDA granted accelerated approval to subcutaneous daratumumab (formulated with hyaluronidase) in combination with bortezomib, cyclophosphamide and dexamethasone for newly diagnosed AL amyloidosis, the first FDA-approved therapy for the disease (Abdallah 2022). The FDA's announcement cites ANDROMEDA hematologic complete response rates of 42.1% vs 13.5% and carries the stage IIIB limitation described under Staging. The 2024 Gertz review describes this four-drug combination as the current first-line therapy with the best outcome.

Daratumumab is a human antibody against CD38, which is found on the clonal plasma cells of AL amyloidosis (Kastritis 2021).

For patients who do not reach at least a VGPR, the Gertz review lists pomalidomide, stem cell transplantation, venetoclax and bendamustine as options for consolidation. The Zanwar review reports that the translocation t(11;14), present in 40% to 60% of AL patients, is linked to poorer response and survival with bortezomib-based therapy, that autologous transplant and daratumumab-based treatment can overcome this, and that it predicts response to venetoclax, which that 2023 review notes was not FDA-approved for this use.

Autologous Stem Cell Transplant (ASCT)

Autologous stem cell transplant uses high-dose melphalan chemotherapy followed by return of the patient's own collected stem cells. The Gertz–Dispenzieri review describes the treatment decision for AL as a choice between high-dose chemotherapy with stem cell transplant and bortezomib-based chemotherapy. Eligibility criteria in the Abdallah and Sanchorawala review generally include biopsy-proven amyloidosis, a plasma cell disorder, involvement of at least one major organ and adequate performance status.

CyBorD and Other Regimens

For transplant-ineligible patients, the Abdallah and Sanchorawala review lists bortezomib-based regimens: bortezomib, oral melphalan and dexamethasone; CyBorD; and subcutaneous daratumumab with CyBorD. The Merlini review credits proteasome inhibitors (such as bortezomib), immunomodulatory drugs, and high-dose chemotherapy with autologous transplant with rapid, deep suppression of light chain production in most patients, and describes effective therapy for advanced cardiac involvement as an unmet need. The Mahmood 2014 review lists melphalan, thalidomide, bortezomib, lenalidomide and bendamustine, each combined with dexamethasone, among the chemotherapy options.

Supportive Care and Heart Transplantation

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Organ Recovery and Long-Term Outcomes

The Merlini review describes early diagnosis as vital to prevent irreversible organ damage. Organ response is the ultimate goal of therapy but typically comes 6 to 12 months after treatment starts, and deeper cardiac and renal responses are associated with longer overall survival (Zanwar 2023).

Monitoring Organ Response

Long-Term Survival in the Modern Era

The Zanwar review reports that overall survival has improved over the past two decades with better plasma cell therapy and supportive care. In the Mayo transplant series, median overall survival was 122 months for all 672 patients and had not been reached for the 2010–2016 cohort (Sidiqi 2018). Even in stage III disease, complete responders had 12- and 24-month survival of 88% and 85%, against 39% and 22% for non-responders (Wechalekar 2013). In the Zanwar review, minimal residual disease negativity by flow cytometry at the end of treatment was associated with longer progression-free survival, with its role still being defined.

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Liver and Gastrointestinal Involvement

The Zanwar review lists the liver and gastrointestinal tract after the heart, kidneys and nerves among commonly involved organs. Kappa-type disease involves the gut and liver more often (Kumar 2010), and in the Comenzo study kappa clones were more likely to present with dominant liver involvement.

Hepatic Amyloidosis

The Zanwar review lists hepatomegaly and a raised alkaline phosphatase as liver presentations, and the Gertz–Dispenzieri review lists unexplained hepatomegaly without imaging abnormalities as a reason to consider amyloidosis. In a series of 80 patients with liver-biopsy-proven AL amyloidosis (Gertz 1988):

Gastrointestinal Amyloidosis

The Zanwar review lists diarrhea from malabsorption, constipation, early satiety and weight loss as gastrointestinal presentations, notes that they are nonspecific, and states that gut involvement can only be confirmed by biopsy.

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Key Research Papers

  1. Kastritis E, Palladini G, Minnema MC, et al. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. N Engl J Med. 2021;385(1):46-58. PubMed PMID: 34192431
  2. Kumar S, Dispenzieri A, Lacy MQ, et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol. 2012;30(9):989-995. PubMed PMID: 22331953
  3. Dispenzieri A, Gertz MA, Kyle RA, et al. Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol. 2004;22(18):3751-3757. PubMed PMID: 15365071
  4. Palladini G, Dispenzieri A, Gertz MA, et al. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012;30(36):4541-4549. PubMed PMID: 23091105
  5. Gertz MA. Immunoglobulin light chain amyloidosis: 2024 update on diagnosis, prognosis, and treatment. Am J Hematol. 2024;99(2):309-324. PubMed PMID: 38095141
  6. Zanwar S, Gertz MA, Muchtar E. Immunoglobulin Light Chain Amyloidosis: Diagnosis and Risk Assessment. J Natl Compr Canc Netw. 2023;21(1):83-90. PubMed PMID: 36630897
  7. Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2021;42(16):1554-1568. PubMed PMID: 33825853
  8. Gertz MA, Dispenzieri A. Systemic Amyloidosis Recognition, Prognosis, and Therapy: A Systematic Review. JAMA. 2020;324(1):79-89. PubMed PMID: 32633805
  9. Merlini G, Dispenzieri A, Sanchorawala V, et al. Systemic immunoglobulin light chain amyloidosis. Nat Rev Dis Primers. 2018;4(1):38. PubMed PMID: 30361521
  10. Palladini G, Hegenbart U, Milani P, et al. A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. Blood. 2014;124(15):2325-2332. PubMed PMID: 25115890
  11. Wechalekar AD, Schonland SO, Kastritis E, et al. A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood. 2013;121(17):3420-3427. PubMed PMID: 23479568
  12. Sidiqi MH, Aljama MA, Buadi FK, et al. Stem Cell Transplantation for Light Chain Amyloidosis: Decreased Early Mortality Over Time. J Clin Oncol. 2018;36(13):1323-1329. PubMed PMID: 29558277
  13. Gertz MA, Lacy MQ, Dispenzieri A, et al. Refinement in patient selection to reduce treatment-related mortality from autologous stem cell transplantation in amyloidosis. Bone Marrow Transplant. 2013;48(4):557-561. PubMed PMID: 22964596
  14. Abdallah M, Sanchorawala V. Update on the Contemporary Treatment of Light Chain Amyloidosis Including Stem Cell Transplantation. Am J Med. 2022;135 Suppl 1:S30-S37. PubMed PMID: 35081382
  15. Mahmood S, Palladini G, Sanchorawala V, Wechalekar A. Update on treatment of light chain amyloidosis. Haematologica. 2014;99(2):209-221. PubMed PMID: 24497558
  16. Quock TP, Yan T, Chang E, et al. Epidemiology of AL amyloidosis: a real-world study using US claims data. Blood Adv. 2018;2(10):1046-1053. PubMed PMID: 29748430
  17. Kourelis TV, Kumar SK, Gertz MA, et al. Coexistent multiple myeloma or increased bone marrow plasma cells define equally high-risk populations in patients with immunoglobulin light chain amyloidosis. J Clin Oncol. 2013;31(34):4319-4324. PubMed PMID: 24145344
  18. Kumar S, Dispenzieri A, Katzmann JA, et al. Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features. Blood. 2010;116(24):5126-5129. PubMed PMID: 20798235
  19. Comenzo RL, Zhang Y, Martinez C, et al. The tropism of organ involvement in primary systemic amyloidosis: contributions of Ig V(L) germ line gene use and clonal plasma cell burden. Blood. 2001;98(3):714-720. PubMed PMID: 11468171
  20. Pepys MB, Herbert J, Hutchinson WL, et al. Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature. 2002;417(6886):254-259. PubMed PMID: 12015594
  21. Hawkins PN, Lavender JP, Pepys MB. Evaluation of systemic amyloidosis by scintigraphy with 123I-labeled serum amyloid P component. N Engl J Med. 1990;323(8):508-513. PubMed PMID: 2377176
  22. Hawkins PN, Wootton R, Pepys MB. Metabolic studies of radioiodinated serum amyloid P component in normal subjects and patients with systemic amyloidosis. J Clin Invest. 1990;86(6):1862-1869. PubMed PMID: 2254450
  23. Muchtar E, Gertz MA, Kumar SK, et al. Digoxin use in systemic light-chain (AL) amyloidosis: contra-indicated or cautious use? Amyloid. 2018;25(2):86-92. PubMed PMID: 29529877
  24. Gertz MA, Falk RH, Skinner M, et al. Worsening of congestive heart failure in amyloid heart disease treated by calcium channel-blocking agents. Am J Cardiol. 1985;55(13 Pt 1):1645. PubMed PMID: 4003314
  25. Pollak A, Falk RH. Left ventricular systolic dysfunction precipitated by verapamil in cardiac amyloidosis. Chest. 1993;104(2):618-620. PubMed PMID: 8339658
  26. Briasoulis A, Stamatelopoulos K, Petropoulos I, et al. Utilization and tolerance of beta-blockers among patients with AL amyloidosis. Amyloid. 2022;29(1):31-37. PubMed PMID: 34549676
  27. Kristen AV, Kreusser MM, Blum P, et al. Improved outcomes after heart transplantation for cardiac amyloidosis in the modern era. J Heart Lung Transplant. 2018;37(5):611-618. PubMed PMID: 29217108
  28. Gertz MA, Kyle RA. Hepatic amyloidosis (primary [AL], immunoglobulin light chain): the natural history in 80 patients. Am J Med. 1988;85(1):73-80. PubMed PMID: 3389383
  29. Gertz MA, Lacy MQ, Dispenzieri A. Amyloidosis: recognition, confirmation, prognosis, and therapy. Mayo Clin Proc. 1999;74(5):490-494. PubMed PMID: 10319082
  30. Dispenzieri A, Buadi F, Kumar SK, et al. Treatment of Immunoglobulin Light Chain Amyloidosis: Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Statement. Mayo Clin Proc. 2015;90(8):1054-1081. PubMed PMID: 26250727
  31. Lousada I, Comenzo RL, Landau H, et al. Light Chain Amyloidosis: Patient Experience Survey from the Amyloidosis Research Consortium. Adv Ther. 2015;32(10):920-928. PubMed PMID: 26498944
  32. Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med. 1997;337(13):898-909. PubMed PMID: 9302305
  33. Sanchorawala V. Light-chain (AL) amyloidosis: diagnosis and treatment. Clin J Am Soc Nephrol. 2006;1(6):1331-1341. PubMed PMID: 17699366
  34. Gillmore JD, Damy T, Fontana M, et al. A new staging system for cardiac transthyretin amyloidosis. Eur Heart J. 2018;39(30):2799-2806. (The ATTR staging system, for comparison.) PubMed PMID: 29048471

The FDA approval date, indication and stage IIIB limitation are from the FDA's announcement (accessed 2026-10-14): FDA accelerated approval of subcutaneous daratumumab for newly diagnosed AL amyloidosis (January 15, 2021).

PubMed Topic Searches

  1. Systematic reviews of autologous stem cell transplantation in AL amyloidosis
  2. AL amyloidosis: pathogenesis and clinical aspects
  3. Diagnosis and management of AL amyloidosis: kidney

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Connections

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