A phase I study of selinexor combined with weekly carfilzomib and dexamethasone in relapsed/refractory multiple myeloma.
clinical trial
multiple myeloma
phase I
Journal
European journal of haematology
ISSN: 1600-0609
Titre abrégé: Eur J Haematol
Pays: England
ID NLM: 8703985
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
revised:
27
01
2023
received:
14
11
2022
accepted:
31
01
2023
medline:
5
4
2023
pubmed:
3
2
2023
entrez:
2
2
2023
Statut:
ppublish
Résumé
We performed a phase I study of weekly selinexor, carfilzomib, and dexamethasone (wSKd) in patients with relapsed/refractory multiple myeloma (MM). The primary objective was to identify the maximum tolerated dose (MTD) of wSKd. Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Prior exposure/refractoriness to carfilzomib was permitted. Thirty patients were enrolled; 26 (87%) had triple-class exposed disease and 6 (20%) received chimeric antigen receptor (CAR) T-cell therapy. Dose level 2 (carfilzomib 70 mg/m
Substances chimiques
carfilzomib
72X6E3J5AR
selinexor
31TZ62FO8F
Dexamethasone
7S5I7G3JQL
Types de publication
Clinical Trial, Phase I
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
564-570Subventions
Organisme : Amgen
Organisme : Karyopharm Therapeutics
Informations de copyright
© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.
Références
Fonseca R, Usmani SZ, Mehra M, et al. Frontline treatment patterns and attrition rates by subsequent lines of therapy in patients with newly diagnosed multiple myeloma. BMC Cancer. 2020;20(1):1087.
Azizian NG, Li Y. XPO1-dependent nuclear export as a target for cancer therapy. J Hematol Oncol. 2020 Jun 1;13(1):61.
Tan DSP, Bedard PL, Kuruvilla J, Siu LL, Razak ARA. Promising SINEs for embargoing nuclear-cytoplasmic export as an anticancer strategy. Cancer Discov. 2014;4(5):527-537.
Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. New England Journal of Medicine. 2019;381(8):727-738.
Kashyap T, Argueta C, Aboukameel A, et al. Selinexor, a selective inhibitor of nuclear export (SINE) compound, acts through NF-κB deactivation and combines with proteasome inhibitors to synergistically induce tumor cell death. Oncotarget. 2016;7(48):78883-78895.
Bahlis NJ, Sutherland H, White D, et al. Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma. Blood. 2018;132(24):2546-2554.
Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. The Lancet. 2020;396(10262):1563-1573.
Ito S. Proteasome inhibitors for the treatment of multiple myeloma. Cancers (Basel). 2020;12(2):265.
Berenson JR, Cartmell A, Bessudo A, et al. CHAMPION-1: a phase 1/2 study of once-weekly carfilzomib and dexamethasone for relapsed or refractory multiple myeloma. Blood. 2016;127(26):3360-3368.
Rosebeck S, Alonge MM, Kandarpa M, et al. Synergistic myeloma cell death via novel intracellular activation of Caspase-10-dependent apoptosis by carfilzomib and selinexor. Mol Cancer Ther. 2016 Jan;15(1):60-71.
Jakubowiak AJ, Jasielec JK, Rosenbaum CA, et al. Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma. Br J Haematol. 2019;186(4):549-560.
Kumar S, Paiva B, Anderson KC, et al. International myeloma working group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328-e346.
Gasparetto C, Schiller GJ, Tuchman SA, et al. Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients. Br J Cancer. 2022 Mar;126(5):718-725.
Wang S, Sellner L, Wang L, et al. Combining selective inhibitors of nuclear export (SINEs) with chimeric antigen receptor (CAR) T cells for CD19-positive malignancies. Oncol Rep. 2021 Aug;46(2):170.