Immune Therapies in AL Amyloidosis—A Glimpse to the Future

Arnon Haran, Iuliana Vaxman, Moshe E. Gatt, Eyal Lebel*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Light-chain (AL) amyloidosis is a rare plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains in target organs, leading to multi-organ dysfunction. Treatment approaches have historically mirrored but lagged behind those of multiple myeloma (MM). Recent advancements in MM immunotherapy are gradually being evaluated and adopted in AL amyloidosis. This review explores the current state of immunotherapeutic strategies in AL amyloidosis, including monoclonal antibodies, antibody–drug conjugates, bispecific antibodies, and chimeric antigen receptor T-cell therapy. We discuss the unique challenges and prospects of these therapies in AL amyloidosis, including the exposure of frail AL amyloidosis patients to immune-mediated toxicities such as cytokine release syndrome (CRS) and immune effector-cell-associated neurotoxicity syndrome (ICANS), as well as their efficacy in promoting rapid and deep hematologic responses. Furthermore, we highlight the need for international initiatives and compassionate programs to provide access to these promising therapies and address critical unmet needs in AL amyloidosis management. Finally, we discuss future directions, including optimizing treatment sequencing and mitigating toxicities, to improve outcomes for AL amyloidosis patients.

Original languageAmerican English
Article number1605
JournalCancers
Volume16
Issue number8
DOIs
StatePublished - Apr 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Keywords

  • amyloidosis
  • bispecific antibodies
  • chimeric antigen receptor T cells
  • immunotherapy
  • light chain
  • plasma cell dyscrasia

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