Management of AL amyloidosis in 2020

Abstract

In amyloid light chain (AL) amyloidosis, a small B-cell clone, most commonly a plasma cell clone, produces monoclonal light chains that exert organ toxicity and deposit in tissue in the form of amyloid fibrils. Organ involvement determines the clinical manifestations, but symptoms are usually recognized late. Patients with disease diagnosed at advanced stages, particularly when heart involvement is present, are at high risk of death within a few months. However, symptoms are always preceded by a detectable monoclonal gammopathy and by elevated biomarkers of organ involvement, and hematologists can screen subjects who have known monoclonal gammopathy for amyloid organ dysfunction and damage, allowing for a presymptomatic diagnosis. Discriminating patients with other forms of amyloidosis is difficult but necessary, and tissue typing with adequate technology available at referral centers, is mandatory to confirm AL amyloidosis. Treatment targets the underlying clone and should be risk adapted to rapidly administer the most effective therapy patients can safely tolerate. In approximately one-fifth of patients, autologous stem cell transplantation can be considered up front or after bortezomib-based conditioning. Bortezomib can improve the depth of response after transplantation and is the backbone of treatment of patients who are not eligible for transplantation. The daratumumab+bortezomib combination is emerging as a novel standard of care in AL amyloidosis. Treatment should be aimed at achieving early and profound hematologic response and organ response in the long term. Close monitoring of hematologic response is vital to shifting nonresponders to rescue treatments. Patients with relapsed/refractory disease are generally treated with immune-modulatory drugs, but daratumumab is also an effective option.

Daratumumab, lenalidomide, and dexamethasone in systemic light‐chain amyloidosis: High efficacy, relevant toxicity and main adverse effect of gain 1q21

“…Efficacy of vaccines against SARS-CoV-2 virus is of great importance to mitigate the Covid-19 pandemic. 1 The BNT162b2 mRNA vaccine (Comirnaty) is the first approved by both FDA and EMA, due to its efficacy in apparently healthy adults. 2 Recently, an assessment of the first vaccination dose effects among nursing facility residents and staff showed that there is some protection after the first injection.…”

“…To the Editor: Daratumumab/dexamethasone (DD) or daratumumab/bortezomib/ dexamethasone (DVD) have become standard salvage regimens in systemic light-chain amyloidosis (AL). 1 Excellent results have been achieved with the combination of daratumumab/lenalidomide/dexamethasone (DRD) in relapsed/refractory and newly diagnosed multiple myeloma (MM). 2 However, in AL the efficacy and toxicity of DRD has not yet been separately assessed.…”

Recent advances in the diagnosis and management of amyloid cardiomyopathy

“…Approximately 20% of AL amyloidosis patients have advanced cardiac involvement at diagnosis (stage IIIb), and treatment of these patients remains an unmet need. Ideally, these patients need a very rapidly acting, safe regimen 93 . The safety profile and rapidity of action of subcutaneous daratumumab make this agent very appealing in this setting, and a phase II trial is currently ongoing (NCT04131309).…”

Systemic AL Amyloidosis and Precision Medicine

“…Other potential but infrequent signs of organ involvement due to amyloid fibrils include hepatomegaly with cholestasis, postural hypotension, syncope, peripheral neuropathy (as ascending, symmetric, small fibers/axonal), gastrointestinal mobility alterations, unintended weight loss, periorbital purpura (i.e., "raccoon eyes"), macroglossia and swelling of the submandibular salivary glands and the shoulder (i.e., "shoulder pad" signs). 8 In symptomatic patients, immunofixation of serum and urine and measurement of FLC have to be performed to check for the presence of monoclonal gammopathy. If a monoclonal protein is present, tissue diagnostic for AL amyloidosis has to be carried out.…”

“…If a monoclonal protein is absent in patients with suspected cardiac amyloidosis, a cardiac scintigraphybased diagnostic pathway with bone tracers is recommended, to look for transthyretin (ATTR) amyloidosis. 8 Molecular genetic analysis is necessary to differentiate between hereditary (rare) and wild-type (frequent) ATTR amyloidosis.…”