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Management of the elderly patient with AL amyloidosis

  • Mario Nuvolone
    Affiliations
    Amyloidosis Research and Treatment Center, Foundation IRCCS Policlinico San Matteo, Department of Molecular Medicine, University of Pavia, Italy
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  • Paolo Milani
    Affiliations
    Amyloidosis Research and Treatment Center, Foundation IRCCS Policlinico San Matteo, Department of Molecular Medicine, University of Pavia, Italy
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  • Giovanni Palladini
    Affiliations
    Amyloidosis Research and Treatment Center, Foundation IRCCS Policlinico San Matteo, Department of Molecular Medicine, University of Pavia, Italy
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  • Giampaolo Merlini
    Correspondence
    Corresponding author at: Amyloidosis Research and Treatment Center, Foundation IRCCS Policlinico San Matteo, Department of Molecular Medicine, University of Pavia, Piazzale Golgi, 2, Pavia 27100, Italy.
    Affiliations
    Amyloidosis Research and Treatment Center, Foundation IRCCS Policlinico San Matteo, Department of Molecular Medicine, University of Pavia, Italy
    Search for articles by this author

      Highlights

      • In AL, frailty is dictated by organ involvement, rather than by chronological age.
      • Given a similar disease stage, elderly AL patients represent often a frailer group.
      • The concept of frailty besides disease stage deserves to be further investigated.
      • Hematologic/organ responses in elderly AL patients do translate in better outcome.

      Abstract

      Systemic immunoglobulin light chain (AL) amyloidosis is an aging-associated protein misfolding and deposition disease. This condition is caused by a small and otherwise indolent plasma cell (or B cell) clone secreting an unstable circulating light chain, which misfolds and deposits as amyloid fibrils possibly leading to progressive dysfunction of affected organs. AL amyloidosis can occur in the typical setting of other, rarer forms of systemic amyloidosis and can mimic other more prevalent conditions of the elderly. Therefore, its diagnosis requires a high degree of clinical suspicion and reliable diagnostic tools for accurate amyloid typing, available at specialized referral centers. In AL amyloidosis, frailty is dictated by the type and severity of organ involvement, with heart involvement being the main determinant of morbidity and mortality. Still, given a similar disease stage, elderly patients with AL amyloidosis are often an even frailer group, due to significant comorbidities, associated disability and polypharmacotherapy, socioeconomic restrictions, and limited access to clinical trials. Recent improvements in the use of biomarkers for early diagnosis, risk stratification and response monitoring, the flourishing of novel, effective anti-plasma cell therapies developed against multiple myeloma and adapted to treat AL amyloidosis, and possibly the introduction of anti-amyloid therapies are rapidly changing the clinical management of this disease and are reflected by improved outcomes. Of note, hematologic and organ responses in elderly patients with AL amyloidosis do translate in better outcome, advocating the importance of treating these patients and striving for a rapid response to therapy also in this challenging clinical setting.

      Keywords

      Abbreviations:

      AA amyloidosis (amyloid A amyloidosis), AL amyloidosis (immunoglobulin light chain amyloidosis), ALP (alkaline phosphatase), ALect2 amyloidosis (leukocyte chemotactic factor 2 amyloidosis), ALP (alkaline phosphatases), ASCT (autologous stem cell transplantation), ATTRm amyloidosis (amyloidosis associated to mutated transthyretin), ATTRwt amyloidosis (amyloidosis associated to wild-type transthyretin), BNP (brain natriuretic peptide), CMR (cardiac magnetic resonance), CR (complete hematologic response), cTnI (cardiac troponin I), cTnT (cardiac troponin T), dFLC (difference between the involved and the uninvolved serum free light chain level), ECG (electrocardiogram), eGFR (estimated glomerular filtration rate), FISH (fluorescent in situ hybridization), GDF-15 (growth differentiation factor-15), Lect2 (leukocyte chemotactic factor 2), LDH (lactate dehydrogenase), MGUS (monoclonal gammopathy of underlying significance), MRD (minimal residual disease), NT-proBNP (amino-terminal pro-brain natriuretic peptide), NYHA (New York Heart Association), PET (positron emission tomography), SAA (serum amyloid A), SAP (serum amyloid P component), sST2 (soluble suppression of tumorigenicity 2), TRAPS (tumor necrosis factor receptor–associated periodic syndrome), TTR (transthyretin), VGPR (very good partial response)
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