PMID- 37743180
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20240410
IS  - 2152-2669 (Electronic)
IS  - 2152-2669 (Linking)
VI  - 23
IP  - 12
DP  - 2023 Dec
TI  - Association of Selinexor Dose Reductions With Clinical Outcomes in the BOSTON 
      Study.
PG  - 917-923.e3
LID - S2152-2650(23)00279-3 [pii]
LID - 10.1016/j.clml.2023.08.018 [doi]
AB  - 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: 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(2)), 
      and twice-weekly dexamethasone (20 mg) were compared between patients with dose 
      reductions and those without. 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: 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.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Jagannath, Sundar
AU  - Jagannath S
AD  - Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY. 
      Electronic address: Sundar.jagannath@mountsinai.org.
FAU - Delimpasi, Sosana
AU  - Delimpasi S
AD  - General Hospital Evangelismos, Athens, Greece.
FAU - Grosicki, Sebastian
AU  - Grosicki S
AD  - Medical University of Silesia, Katowice, Poland.
FAU - Van Domelen, Dane R
AU  - Van Domelen DR
AD  - Karyopharm Therapeutics Inc., Newton, MA.
FAU - Bentur, Ohad S
AU  - Bentur OS
AD  - Karyopharm Therapeutics Inc., Newton, MA.
FAU - Spicka, Ivan
AU  - Spicka I
AD  - Charles University and General Hospital, Prague, Czech Republic.
FAU - Dimopoulos, Meletios A
AU  - Dimopoulos MA
AD  - National and Kapodistrian University of Athens School of Medicine, Athens, 
      Greece.
LA  - eng
SI  - ClinicalTrials.gov/NCT03110562
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230829
PL  - United States
TA  - Clin Lymphoma Myeloma Leuk
JT  - Clinical lymphoma, myeloma & leukemia
JID - 101525386
RN  - 31TZ62FO8F (selinexor)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Humans
MH  - *Quality of Life
MH  - Drug Tapering
MH  - Dexamethasone/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - *Multiple Myeloma/drug therapy
OTO - NOTNLM
OT  - Adverse events
OT  - Multiple myeloma
OT  - Quality of life
OT  - Response
COIS- 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.
EDAT- 2023/09/25 00:42
MHDA- 2023/11/27 12:43
CRDT- 2023/09/24 21:56
PHST- 2023/08/02 00:00 [received]
PHST- 2023/08/24 00:00 [accepted]
PHST- 2023/11/27 12:43 [medline]
PHST- 2023/09/25 00:42 [pubmed]
PHST- 2023/09/24 21:56 [entrez]
AID - S2152-2650(23)00279-3 [pii]
AID - 10.1016/j.clml.2023.08.018 [doi]
PST - ppublish
SO  - Clin Lymphoma Myeloma Leuk. 2023 Dec;23(12):917-923.e3. doi: 
      10.1016/j.clml.2023.08.018. Epub 2023 Aug 29.