Comprehensive Review of AL amyloidosis: some practical recommendations

Abstract

Amyloid light chain (AL) amyloidosis is among the more common and more severe of the amyloidoses usually involving the slow proliferation of a bone-marrow-residing plasma cell (PC) clone and the secretion of unstable immunoglobulin-free light chains (FLC) that infiltrate peripheral tissues and result in detrimental end-organ damage. Disease presentation is rather vague, and the hallmark of treatment is early diagnosis before irreversible end-organ damage. Once diagnosed, treatment decision is transplant-driven whereby ~20% of patients are eligible for autologous stem cell transplantation (ASCT) with or without bortezomib-based induction. In the setting of ASCT-ineligibility, bortezomib plays a central role in upfront treatment with the recent addition of daratumumab to the current emerging standard of care. In general, management of AL amyloidosis is aimed at achieving deep, durable responses with very close monitoring for early detection of relapse/refractory disease. This article provides a comprehensive review of the management of patients with AL amyloidosis including goals of therapy, current treatment guidelines in the setting of both ASCT-eligibility and ineligibility, treatment response monitoring recommendations, toxicity management, and treatment of relapse/refractory disease.

Fig. 1. Monitoring, presenting symptoms, anddiagnosis of AL amyloidosis.

MGUS monoclonal gammopathy of undetermined significance, NT-proBNP N-terminal pro b-type natriuretic peptide.

Fig. 2. Treatment algorithm for AL amyloidosis.

ASCT autologous stem cell transplantation, ECOG Eastern Cooperative Oncology Group, NYHA New York Heart Association classification of the extent of heart failure, LVEF left ventricular ejection fraction, SBP systolic blood pressure, TnT troponin T, CrCl creatinine clearance, DLCO diffusion capacity of the lungs for carbon monoxide, BMPC bone marrow plasmacytosis, IMiD immunomodulatory imide drugs, PI proteosome inhibitors, OS overall survival, G-CSF granulocyte colony-stimulating factor, CR complete remission, PFS progression-free survival, ESRD end-stage renal disease, ORR overall response rate.

Fig. 3. Criteria for hematologic and organ response in amyloidosis.

SPEP/IFE serum protein electrophoresis and immunofixation, UPEP/IFE urine protein electrophoresis and immunofixation, dFLC delta free light chain, uFLC uninvolved free light chain, eGFR estimated glomerular filtration rate, CHOR composite hematologic/organ response model. Response criteria were derived from Palladini et al. J. Clin. Oncol 2012; Comenzo et al. Leukemia 2012; and Palladini et al. Blood 2014. a: New BNP-based cardiac criteria were derived from Lilleness et al. BJH 2020. CHOR scoring model derived from Sidana et al. Blood Cancer Journal 2020.