Diagnosis and treatment guidelinesTreatment of Immunoglobulin Light Chain Amyloidosis: Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Statement
Section snippets
Diagnosis of AL Amyloidosis
The diagnostic biopsy sample may be from the tissue causing symptoms—eg, heart or kidney—or from a more accessible tissue, such as subcutaneous fat or bone marrow. The sensitivity of a biopsy sample from a symptomatic organ is higher than that from the more accessible tissues, ie, more than 95% for a symptomatic organ, 75% to 80% for fat, and 50% to 65% for bone marrow.10 Special stains, such as Congo red, thioflavin T, and sulfated alcian blue, are required to recognize amyloidosis. The gold
Tumor/Precursor Protein Burden
Screening for a monoclonal protein is done by serum immunoglobulin free light chain measurement and immunofixation studies of the serum and urine.17 The distribution of immunoglobulin light chain variable gene use by bone marrow plasma cells is expected to be 2 to 1 κ to λ in the healthy population. Despite this, the number of AL amyloidosis cases favors λ to κ by 2 to 1, which supports the concept that germline λ is intrinsically more amyloidogenic than κ. A bone marrow aspirate to determine
Prognosis of AL Amyloidosis
The prognosis of patients with AL amyloidosis depends on the burden of the amyloid in the tissues (especially the heart) and the size of the plasma cell clone and its biology, which predict the ability to achieve a hematologic and organ response (Table 2).41, 42 Cardiac involvement predicts most early deaths. Plasma cell biology predicts deaths occurring after the first year. During the past 40 years, the proportion of patients dying within 12 months of diagnosis remains fixed at approximately
Prognostic Impact of Cardiac Involvement
The extent of cardiac involvement drives prognosis more than any other organ involvement, although symptomatic hepatic involvement and autonomic involvement also influence survival.54 Soluble cardiac biomarkers have been accepted by the amyloid community as the best means by which to stage patients with AL amyloidosis; the most commonly used biomarkers include troponin T and NT-proBNP (Table 3).26, 27, 28, 29, 30, 31, 32, 33, 34, 35 Potential advantages of blood tests for assessing cardiac
Rationale for the Recommendations
Any recommendation for the treatment of AL amyloidosis is confounded by the disease’s intrinsic heterogeneity, its rarity, and the paucity of randomized clinical trials. Despite these challenges, we believe that the combination of the literature and the experience of the authors, who are experts in the field, make these recommendations sound. Clinical trials should always be considered the first choice when available. In the absence of clinical trials, recommendations are as discussed herein (
Guideline
Treatment should be initiated immediately in virtually all patients with systemic AL amyloidosis.
Initial Therapy for Patients With Systemic AL Amyloidosis
Clinical trials should always be considered in the frontline setting if available. In the absence of clinical trials, recommendations are as discussed herein.
Initial Therapy for Patients Ineligible for SCT
Clinical trials are again the preferred strategy; however, in the absence of a trial, a variety of options can be considered.
Regimen
Rituxan, bortezomib, and dexamethasone.
Guideline
Potential benefit as first line therapy.
Grade of Recommendation
B
Regimen
CyBorD as first line
Guideline
Potential benefit as first line therapy.
Grade of Recommendation
B
IgM-associated AL amyloidosis is a rare clinical entity with distinctive clinical characteristics. Many cases may be localized forms, in which there is only nodal or soft-tissue involvement without visceral involvement. Many of these cases can merely be observed, but observed more aggressively if there is a circulating monoclonal protein and especially
Guideline
Base salvage therapies on previous therapies, with the aim of introducing drugs with other mechanisms of action to treat relapsed or refractory AL amyloidosis.
Guideline
Diuretics are the mainstay of supportive care for cardiac AL amyloidosis.
Guideline
β-Blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and calcium channel blockers should be used with great caution (or not at all) in cardiac AL amyloidosis.
Organ Transplant
Solid organ transplant is a controversial intervention in patients with AL amyloidosis. Because the disease is systemic and presumably incurable, there is concern that the amyloid will either reoccur in the transplanted organ or progress in another organ, resulting in a poor outcome. The best outcomes have occurred in the setting of careful patient selection, excluding patients with clinically evident multiorgan involvement, and in those who received chemotherapy to eradicate the clone either
Treating Localized Amyloidosis
The location of the amyloid is an important clue in recognizing the amyloid as being localized. The most frequent sites of localized amyloid are the respiratory tract, genitourinary tract, and skin.13 Pulmonary amyloid can be subdivided into nodular, laryngeal/tracheobronchial, and diffuse interstitial. Only the third type represents a manifestation of systemic AL amyloidosis.196, 197 The nodular form of amyloid presents as solitary pulmonary nodules or multiple nodules. This does not represent
Future Directions
There is unprecedented interest in AL amyloidosis, which has resulted in improved outcomes for these patients. Clearly, more work needs to be done, especially in the realms of earlier diagnosis, salvaging the 35% of patients who seem destined to die within the first 6 months of diagnosis, and more innovative therapies. Physicians caring for patients with AL amyloidosis have been borrowing and customizing therapies used for patients with MM with varying degrees of success. One of the biggest
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Cited by (0)
Grant Support: This work was supported in part by the Robert A. Kyle Hematologic Malignancies Program, the Jabbs Foundation, and the Predolin Foundation.
Potential Competing Interests: Dr Dispenzieri has received research support from Celgene, Millenium, Pfizer, Jannsen, and Alnylam. Dr Kumar as received research support from Celgene, Novartis, Onyx, Millennium, Sanofi, and Janssen. Dr Reeder has received research support from Celgene, Novartis, and Millennium. Dr Mikhael has received research support from Celgene, Onyx, Abbvie, and Sanofi. Dr Grogan has received research support from Pfizer; and consulting fees from Prothena. Dr Fonseca has a patent for the prognostication of multiple myeloma based on genetic categorization of the disease; has received consulting fees from Celgene, Genzyme, BMS, Bayer, Lilly, Onyx, Binding Site, Novartis, Sanofi, Millennium, and AMGEN; has sponsored research from Onyx; and is a member of the scientific advisory board of Applied Biosciences. Dr Ailawadhi has received honoraria from Millennium and Amgen. Dr Bergsagel has received research support from Novartis and Constellation Pharmaceuticals; and consultant fees from Amgen, Janssen, Sanofi-Aventis, Mundipharma, and BMS. Dr Stewart has received research support from Celgene and Millennium Pharmaceuticals; and consulting fees from Novartis and Millennium Pharmaceuticals. Dr Gertz has received research support from ISIS and Prothena; and honoraria from Celgene, Millennium Pharmaceuticals, and Novartis.