Combined Proteasome and Autophagy Inhibition in Relapsed/Refractory Multiple Myeloma—A Phase I Trial of Hydroxychloroquine, Carfilzomib, and Dexamethasone

Combined Proteasome and Autophagy Inhibition in Relapsed/Refractory Multiple Myeloma—A Phase I Trial of Hydroxychloroquine, Carfilzomib, and Dexamethasone

ABSTRACT Multiple myeloma is characterized by malignant cells which produce high amounts of monoclonal immunoglobulin. Myeloma cells are, therefore, dependent on effective protein degradation. Proteasomal protein degradation is targeted by proteasome inhibitors in routine care. Autophagic protein de...

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Main Authors: Tobias S. Slørdahl, Frida Bugge Askeland, Margrete Sofie Sætre Hanssen, Håkon Hov, Stine Marie Sundt‐Hansen, Sofia Lindahl, Nils Tore Vethe, Henrik Hjorth‐Hansen, Mona H. Fenstad, Anders Waage, Øyvind Hjertner, Fredrik Schjesvold, Anders Sundan
Format: Article
Language:English
Published: Wiley 2025-02-01
Series:eJHaem
Subjects:
autophagy
multiple myeloma
myeloma
myeloma therapy
Online Access:https://doi.org/10.1002/jha2.1091
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Summary:ABSTRACT Multiple myeloma is characterized by malignant cells which produce high amounts of monoclonal immunoglobulin. Myeloma cells are, therefore, dependent on effective protein degradation. Proteasomal protein degradation is targeted by proteasome inhibitors in routine care. Autophagic protein degradation is currently not targeted in myeloma treatment. This Phase I trial showed that the combination of the proteasome inhibitor carfilzomib and the autophagy inhibitor hydroxychloroquine was well tolerated in patients with relapsed/refractory multiple myeloma. Adverse events were mostly Grades 1 and 2. An overall response rate of 44% indicates a meaningful clinical efficacy of this combination. Trial Registration: The study was registered at clinicaltrials.gov # NCT04163107.
ISSN:2688-6146

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