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Beyond Andromeda: Improving Therapy for Light Chain Amyloidosis

Therapy for light chain amyloidosis (AL) continues to evolve, and a new standard of care for the disease is rapidly forming. The risk of early death however, mainly from cardiac complications, remains an important benchmark yet to be definitively improved upon. This brief review explores recent adva...

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Detalles Bibliográficos
Autores principales: Kaufman, Gregory P., Cerchione, Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888257/
https://www.ncbi.nlm.nih.gov/pubmed/33614504
http://dx.doi.org/10.3389/fonc.2020.624573
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author Kaufman, Gregory P.
Cerchione, Claudio
author_facet Kaufman, Gregory P.
Cerchione, Claudio
author_sort Kaufman, Gregory P.
collection PubMed
description Therapy for light chain amyloidosis (AL) continues to evolve, and a new standard of care for the disease is rapidly forming. The risk of early death however, mainly from cardiac complications, remains an important benchmark yet to be definitively improved upon. This brief review explores recent advances in plasma cell directed therapy for AL, highlighting unique factors specific to these patients and AL biology driving differences in treatment strategies and clinical development compared with multiple myeloma. Improving upon proteasome inhibitor based upfront therapy combinations with the addition of anti-CD38 antibodies has shown promise with improved response rates in the ANDROMEDA (NCT03201965) study. Though depth and kinetics of achieving deep hematologic response as well as rates of biomarker defined organ response were improved with the addition of daratumumab to the combination of bortezomib, cyclophosphamide, and dexamethasone, death rates in each arm remained similar. Evaluation of other targeted and novel therapies in AL is ongoing, and we highlight efforts evaluating B-cell maturation antigen (BCMA) directed therapy, BCL-2 family inhibitors, and other novel agents in the field. We also look ahead to efforts to reimagine the clinical development of anti-fibrillar therapies after late phase study failures. Upcoming anti-amyloid fibril antibody studies explore opportunities to improve outcomes for the sickest AL patients with advanced cardiac disease, focusing on improving overall patient survival and reducing the risk of early death in this uniquely frail population.
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spelling pubmed-78882572021-02-18 Beyond Andromeda: Improving Therapy for Light Chain Amyloidosis Kaufman, Gregory P. Cerchione, Claudio Front Oncol Oncology Therapy for light chain amyloidosis (AL) continues to evolve, and a new standard of care for the disease is rapidly forming. The risk of early death however, mainly from cardiac complications, remains an important benchmark yet to be definitively improved upon. This brief review explores recent advances in plasma cell directed therapy for AL, highlighting unique factors specific to these patients and AL biology driving differences in treatment strategies and clinical development compared with multiple myeloma. Improving upon proteasome inhibitor based upfront therapy combinations with the addition of anti-CD38 antibodies has shown promise with improved response rates in the ANDROMEDA (NCT03201965) study. Though depth and kinetics of achieving deep hematologic response as well as rates of biomarker defined organ response were improved with the addition of daratumumab to the combination of bortezomib, cyclophosphamide, and dexamethasone, death rates in each arm remained similar. Evaluation of other targeted and novel therapies in AL is ongoing, and we highlight efforts evaluating B-cell maturation antigen (BCMA) directed therapy, BCL-2 family inhibitors, and other novel agents in the field. We also look ahead to efforts to reimagine the clinical development of anti-fibrillar therapies after late phase study failures. Upcoming anti-amyloid fibril antibody studies explore opportunities to improve outcomes for the sickest AL patients with advanced cardiac disease, focusing on improving overall patient survival and reducing the risk of early death in this uniquely frail population. Frontiers Media S.A. 2021-02-03 /pmc/articles/PMC7888257/ /pubmed/33614504 http://dx.doi.org/10.3389/fonc.2020.624573 Text en Copyright © 2021 Kaufman and Cerchione http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Kaufman, Gregory P.
Cerchione, Claudio
Beyond Andromeda: Improving Therapy for Light Chain Amyloidosis
title Beyond Andromeda: Improving Therapy for Light Chain Amyloidosis
title_full Beyond Andromeda: Improving Therapy for Light Chain Amyloidosis
title_fullStr Beyond Andromeda: Improving Therapy for Light Chain Amyloidosis
title_full_unstemmed Beyond Andromeda: Improving Therapy for Light Chain Amyloidosis
title_short Beyond Andromeda: Improving Therapy for Light Chain Amyloidosis
title_sort beyond andromeda: improving therapy for light chain amyloidosis
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888257/
https://www.ncbi.nlm.nih.gov/pubmed/33614504
http://dx.doi.org/10.3389/fonc.2020.624573
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