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2018 ; 3
(3
): 530-541
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Novel Therapies in Light Chain Amyloidosis
#MMPMID29854961
Milani P
; Merlini G
; Palladini G
Kidney Int Rep
2018[May]; 3
(3
): 530-541
PMID29854961
show ga
Light chain (AL) amyloidosis is the most common form of amyloidosis involving the
kidney. It is characterized by albuminuria, progressing to overt nephrotic
syndrome and eventually end-stage renal failure if diagnosed late or
ineffectively treated, and in most cases by concomitant heart involvement.
Cardiac amyloidosis is the main determinant of survival, whereas the risk of
dialysis is predicted by baseline proteinuria and glomerular filtration rate, and
by response to therapy. The backbone of treatment is chemotherapy targeting the
underlying plasma cell clone, that needs to be risk-adapted due to the frailty of
patients with AL amyloidosis who have cardiac and/or multiorgan involvement.
Low-risk patients (?20%) can be considered for autologous stem cell
transplantation that can be preceded by induction and/or followed by
consolidation with bortezomib-based regimens. Bortezomib combined with
alkylators, such as melphalan, preferred in patients harboring t(11;14), or
cyclophosphamide, is used in most intermediate-risk patients, and with cautious
dose escalation in high-risk subjects. Novel, powerful anti-plasma cell agents,
such as pomalidomide, ixazomib, and daratumumab, prove effective in the
relapsed/refractory setting, and are being moved to upfront therapy in clinical
trials. Novel approaches based on small molecules interfering with the
amyloidogenic process and on antibodies targeting the amyloid deposits gave
promising results in preliminary uncontrolled studies, are being tested in
controlled trials, and will likely prove powerful complements to chemotherapy.
Finally, improvements in the understanding of the molecular mechanisms of organ
damage are unveiling novel potential treatment targets, moving toward a cure for
this dreadful disease.
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