GIAMPAOLO MERLINI (PAVIA)
CASE-BASED LECTURE: HOW I TREAT AMYLOIDOSIS
Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo,
Department of Molecular Medicine, University of Pavia, Italy.
The clinical presentation of AL amyloidosis is protean and deceptive, and symptoms are often misinterpreted
and recognized late. When they appear, organ involvement is often advanced, however, biomarkers and
imaging may allow early diagnosis. Since AL amyloidosis is associated with significant multiorgan dysfunction
and patient frailty, treatment delivery requires caution. Thus, treatment strategy needs to be risk-adapted
based on the severity of organ dysfunction, age, and comorbidities 1. The current treatment of AL amyloidosis
targets the underlying clonal disease to reduce the supply of the amyloid light chain. Other approaches,
targeting the amyloid deposits are under investigation2. It is largely recognized that rapid and deep
reductions of the circulating amyloid light chains are key to improve organ dysfunction and extend survival
3. This is true also in high-risk patients 4. Thus, treatment of AL amyloidosis needs to be response-adapted,
and patients should be followed closely during chemotherapy, to detect early those who fail to reach a
satisfactory hematologic response and promptly start a rescue therapy. Response criteria are under revision
5. The outcome of the recently completed randomized phase III ANDROMEDA trial of daratumumab in
upfront treatment of patients with AL amyloidosis showed that the combination of CyBorD with
daratumumab is very effective and well tolerated6. This combination represents now the standard of care
for frontline therapy. Patients with relapsed/refractory disease are generally treated with immune-modulatory
drugs, but daratumumab and venetoclax7 are also effective options.
The case presented highlights the persisting diagnostic hurdles, and the treatment challenges.
1. Palladini G, Milani P, Merlini G. Management of AL amyloidosis in 2020. Blood. 2020;136(23):2620-2627.
2. Merlini G, Dispenzieri A, Sanchorawala V, et al. Systemic immunoglobulin light chain amyloidosis. Nat Rev
Dis Primers. 2018;4(1):38.
3. Palladini G, Lavatelli F, Russo P, et al. Circulating amyloidogenic free light chains and serum N-terminal
natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL. Blood.
2006;107(10):3854-3858.
4. Manwani R, Foard D, Mahmood S, et al. Rapid hematologic responses improve outcomes in patients with
very advanced (stage IIIb) cardiac immunoglobulin light chain amyloidosis. Haematologica. 2018;103(4):e165-
e168.
5. Muchtar E, Dispenzieri A, Leung N, et al. Depth of organ response in AL amyloidosis is associated with
improved survival: grading the organ response criteria. Leukemia. 2018;32(10):2240-2249.
6. Comenzo RL, Kastritis E, Palladini G, et al. Reduction in Absolute Involved Free Light Chain and Difference
between Involved and Uninvolved Free Light Chain Is Associated with Prolonged Major Organ Deterioration
Progression-Free Survival in Patients with Newly Diagnosed AL Amyloidosis Receiving Bortezomib,
Cyclophosphamide, and Dexamethasone with or without Daratumumab: Results from Andromeda. Blood.
2020;136(Supplement 1):48-50.
7. Premkumar VJ, Lentzsch S, Pan S, et al. Venetoclax induces deep hematologic remissions in t(11;14)
relapsed/refractory AL amyloidosis. Blood Cancer J. 2021;11(1):10.