Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients.
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Dexamethasone
/ administration & dosage
Drug Administration Schedule
Female
Humans
Hydrazines
/ administration & dosage
Male
Maximum Tolerated Dose
Middle Aged
Multiple Myeloma
/ drug therapy
Oligopeptides
/ administration & dosage
Survival Analysis
Translocation, Genetic
Treatment Outcome
Triazoles
/ administration & dosage
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
14
07
2021
accepted:
20
10
2021
pubmed:
22
11
2021
medline:
11
3
2022
entrez:
21
11
2021
Statut:
ppublish
Résumé
Proteasome inhibitors (PIs), including carfilzomib, potentiate the activity of selinexor, a novel, first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in preclinical models of multiple myeloma (MM). The safety, efficacy, maximum-tolerated dose (MTD) and recommended phase 2 dose (RP2D) of selinexor (80 or 100 mg) + carfilzomib (56 or 70 mg/m Thirty-two patients, median prior therapies 4 (range, 1-8), were enrolled. MM was triple-class refractory in 38% of patients and 53% of patients had high-risk cytogenetics del(17p), t(4;14), t(14;16) and/or gain 1q. Common treatment-related adverse events (all/Grade 3) were thrombocytopenia 72%/47% (G3 and G4), nausea 72%/6%, anaemia 53%/19% and fatigue 53%/9%, all expected and manageable with supportive care and dose modifications. MTD and RP2D were identified as selinexor 80 mg, carfilzomib 56 mg/m Weekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM.
Sections du résumé
BACKGROUND
Proteasome inhibitors (PIs), including carfilzomib, potentiate the activity of selinexor, a novel, first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in preclinical models of multiple myeloma (MM).
METHODS
The safety, efficacy, maximum-tolerated dose (MTD) and recommended phase 2 dose (RP2D) of selinexor (80 or 100 mg) + carfilzomib (56 or 70 mg/m
RESULTS
Thirty-two patients, median prior therapies 4 (range, 1-8), were enrolled. MM was triple-class refractory in 38% of patients and 53% of patients had high-risk cytogenetics del(17p), t(4;14), t(14;16) and/or gain 1q. Common treatment-related adverse events (all/Grade 3) were thrombocytopenia 72%/47% (G3 and G4), nausea 72%/6%, anaemia 53%/19% and fatigue 53%/9%, all expected and manageable with supportive care and dose modifications. MTD and RP2D were identified as selinexor 80 mg, carfilzomib 56 mg/m
CONCLUSIONS
Weekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM.
Identifiants
pubmed: 34802051
doi: 10.1038/s41416-021-01608-2
pii: 10.1038/s41416-021-01608-2
pmc: PMC8605887
doi:
Substances chimiques
Hydrazines
0
Oligopeptides
0
Triazoles
0
selinexor
31TZ62FO8F
carfilzomib
72X6E3J5AR
Dexamethasone
7S5I7G3JQL
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
718-725Informations de copyright
© 2021. The Author(s).
Références
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