EJHaem · 2025
Combined Proteasome and Autophagy Inhibition in Relapsed/Refractory Multiple Myeloma-A Phase I Trial of Hydroxychloroquine, Carfilzomib, and Dexamethasone.
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Slørdahl Tobias S, Askeland Frida Bugge, Hanssen Margrete Sofie Sætre, Hov Håkon, Sundt-Hansen Stine Marie, Lindahl Sofia, Vethe Nils Tore, Hjorth-Hansen Henrik, Fenstad Mona H, Waage Anders, Hjertner Øyvind, Schjesvold Fredrik, Sundan Anders
Аннотация
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.