Association of Selinexor Dose Reductions With Clinical Outcomes in the BOSTON Study.


Journal

Clinical lymphoma, myeloma & leukemia
ISSN: 2152-2669
Titre abrégé: Clin Lymphoma Myeloma Leuk
Pays: United States
ID NLM: 101525386

Informations de publication

Date de publication:
Dec 2023
Historique:
received: 02 08 2023
accepted: 24 08 2023
medline: 27 11 2023
pubmed: 25 9 2023
entrez: 24 9 2023
Statut: ppublish

Résumé

Dose modifications in response to adverse events (AEs) can maintain tumor response and improve therapy tolerability. We conducted a post-hoc analysis of the efficacy and safety of reduced selinexor doses in the BOSTON trial (NCT03110562). Efficacy, safety, and quality of life (QoL) in 195 patients with relapsed/refractory multiple myeloma randomized to once-weekly (QW) selinexor (100 mg), QW subcutaneous bortezomib (1.3 mg/m In total, 126 patients (65%) had selinexor dose reductions (median dose 71.4 mg/wk). In patients with dose reductions versus those without median progression-free survival was 16.6 months (95% CI 12.9-not evaluable [NE]) versus 9.2 months [95% CI 6.8-15.5]), overall response rate was 81.7% (95% CI 73.9-88.1%) versus 66.7% (95% CI 54.3-77.6%), ≥very good partial response was (51.6% [95% CI 42.5-60.6%] vs. 31.9% [95% CI 21.2-44.2]), median duration of response was not reached (95% CI 13.8-NE) versus 12.0 months (95% CI 8.3-NE), and time to next treatment was 22.6 months (95% CI 14.6-NE) versus 10.5 months (95% CI 6.3-18.2). Mean best change from baseline on the EORTC QLQ-C30 Global Health Status/QoL scale was 10.0 ± 20.5 versus 4.0 ± 20.9. Duration-adjusted AE rates that were lower after selinexor dose reduction included thrombocytopenia (62.5% before vs. 47.6% after), nausea (31.6% vs. 7.3%), fatigue (28.1% vs. 9.9%), decreased appetite (21.5% vs. 6.4%), anemia (17.9% vs. 10.3%), and diarrhea (12.9% vs. 5.2%). Appropriate dose reductions in response to AEs of the 100 mg selinexor starting dose in the BOSTON study were associated with improved efficacy, reduced AE rates and improved QoL.

Sections du résumé

BACKGROUND BACKGROUND
Dose modifications in response to adverse events (AEs) can maintain tumor response and improve therapy tolerability. We conducted a post-hoc analysis of the efficacy and safety of reduced selinexor doses in the BOSTON trial (NCT03110562).
PATIENTS AND METHODS METHODS
Efficacy, safety, and quality of life (QoL) in 195 patients with relapsed/refractory multiple myeloma randomized to once-weekly (QW) selinexor (100 mg), QW subcutaneous bortezomib (1.3 mg/m
RESULTS RESULTS
In total, 126 patients (65%) had selinexor dose reductions (median dose 71.4 mg/wk). In patients with dose reductions versus those without median progression-free survival was 16.6 months (95% CI 12.9-not evaluable [NE]) versus 9.2 months [95% CI 6.8-15.5]), overall response rate was 81.7% (95% CI 73.9-88.1%) versus 66.7% (95% CI 54.3-77.6%), ≥very good partial response was (51.6% [95% CI 42.5-60.6%] vs. 31.9% [95% CI 21.2-44.2]), median duration of response was not reached (95% CI 13.8-NE) versus 12.0 months (95% CI 8.3-NE), and time to next treatment was 22.6 months (95% CI 14.6-NE) versus 10.5 months (95% CI 6.3-18.2). Mean best change from baseline on the EORTC QLQ-C30 Global Health Status/QoL scale was 10.0 ± 20.5 versus 4.0 ± 20.9. Duration-adjusted AE rates that were lower after selinexor dose reduction included thrombocytopenia (62.5% before vs. 47.6% after), nausea (31.6% vs. 7.3%), fatigue (28.1% vs. 9.9%), decreased appetite (21.5% vs. 6.4%), anemia (17.9% vs. 10.3%), and diarrhea (12.9% vs. 5.2%).
CONCLUSION CONCLUSIONS
Appropriate dose reductions in response to AEs of the 100 mg selinexor starting dose in the BOSTON study were associated with improved efficacy, reduced AE rates and improved QoL.

Identifiants

pubmed: 37743180
pii: S2152-2650(23)00279-3
doi: 10.1016/j.clml.2023.08.018
pii:
doi:

Substances chimiques

selinexor 31TZ62FO8F
Dexamethasone 7S5I7G3JQL

Banques de données

ClinicalTrials.gov
['NCT03110562']

Types de publication

Randomized Controlled Trial Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

917-923.e3

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure Sundar Jagannath: consultation: Janssen, Bristol Myers Squibb, Sanofi, Regeneron, Takeda, and Caribou. Sosana Delimpasi: Speaker: Janssen, Bristol Myers Squibb, Amgen, Sanofi, GSK, and Takeda. Meletios A. Dimopoulos: honoraria for participation in advisory boards: Abbvie, Amgen, Bristol Myers Squibb, Beigene Inc, GSK, Janssen, Menarini, Regeneron, Sanofi and Takeda. Ohad S. Bentur and Dane R. Van Domelen: employment and equity holders: Karyopharm. The remaining authors have no conflicts of interest to disclose.

Auteurs

Sundar Jagannath (S)

Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: Sundar.jagannath@mountsinai.org.

Sosana Delimpasi (S)

General Hospital Evangelismos, Athens, Greece.

Sebastian Grosicki (S)

Medical University of Silesia, Katowice, Poland.

Dane R Van Domelen (DR)

Karyopharm Therapeutics Inc., Newton, MA.

Ohad S Bentur (OS)

Karyopharm Therapeutics Inc., Newton, MA.

Ivan Špička (I)

Charles University and General Hospital, Prague, Czech Republic.

Meletios A Dimopoulos (MA)

National and Kapodistrian University of Athens School of Medicine, Athens, Greece.

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