PMID- 36726221
OWN - NLM
STAT- MEDLINE
DCOM- 20230405
LR  - 20230405
IS  - 1600-0609 (Electronic)
IS  - 0902-4441 (Linking)
VI  - 110
IP  - 5
DP  - 2023 May
TI  - A phase I study of selinexor combined with weekly carfilzomib and dexamethasone 
      in relapsed/refractory multiple myeloma.
PG  - 564-570
LID - 10.1111/ejh.13937 [doi]
AB  - 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(2) Intravenous [IV] on Days 1, 8, and 15; selinexor 
      100 mg PO on Days 1, 8, 15, 22; dexamethasone 40 mg on Days 1, 8, 15, 22 of 
      28-day cycles) was chosen as the MTD, with no DLTs having occurred. The most 
      common hematologic adverse events (AE) were thrombocytopenia (83%), anemia (70%), 
      lymphopenia (50%), and neutropenia (50%). The most common nonhematologic AE were 
      fatigue (70%), nausea (70%), diarrhea (53%), and anorexia (47%). The ORR was 
      21/30 (70%) overall and 18/23 (78%) at the MTD. At a median follow-up of 
      12.3 months, the median PFS was 5.3 months and median OS 23.3 months. Responses 
      were similar in carfilzomib naive and exposed patients. Long-term efficacy of 
      wSKd is modest; wSKd could be employed as a bridging strategy to immunotherapies.
CI  - (c) 2023 The Authors. European Journal of Haematology published by John Wiley & 
      Sons Ltd.
FAU - Derman, Benjamin A
AU  - Derman BA
AUID- ORCID: 0000-0002-4070-1819
AD  - Section of Hematology/Oncology, Chicago, Illinois, USA.
FAU - Chari, Ajai
AU  - Chari A
AD  - Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New 
      York, New York, USA.
FAU - Zonder, Jeffrey
AU  - Zonder J
AUID- ORCID: 0000-0002-1741-2795
AD  - Division of Hematology/Oncology, Karmanos Cancer Institute, Wayne State 
      University, Detroit, Michigan, USA.
FAU - Major, Ajay
AU  - Major A
AUID- ORCID: 0000-0001-7261-1335
AD  - Section of Hematology/Oncology, Chicago, Illinois, USA.
AD  - Division of Hematology, University of Colorado School of Medicine, Denver, 
      Colorado, USA.
FAU - Stefka, Andrew T
AU  - Stefka AT
AUID- ORCID: 0000-0002-7651-3430
AD  - Section of Hematology/Oncology, Chicago, Illinois, USA.
FAU - Jiang, Ken
AU  - Jiang K
AD  - Section of Hematology/Oncology, Chicago, Illinois, USA.
FAU - Karrison, Theodore
AU  - Karrison T
AD  - Section of Hematology/Oncology, Chicago, Illinois, USA.
FAU - Jasielec, Jagoda
AU  - Jasielec J
AD  - Section of Hematology/Oncology, Chicago, Illinois, USA.
FAU - Jakubowiak, Andrzej
AU  - Jakubowiak A
AUID- ORCID: 0000-0002-2597-6822
AD  - Section of Hematology/Oncology, Chicago, Illinois, USA.
LA  - eng
GR  - Amgen/
GR  - Karyopharm Therapeutics/
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20230215
PL  - England
TA  - Eur J Haematol
JT  - European journal of haematology
JID - 8703985
RN  - 72X6E3J5AR (carfilzomib)
RN  - 31TZ62FO8F (selinexor)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Humans
MH  - *Multiple Myeloma/diagnosis/drug therapy
MH  - Dexamethasone
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
OTO - NOTNLM
OT  - clinical trial
OT  - multiple myeloma
OT  - phase I
EDAT- 2023/02/03 06:00
MHDA- 2023/04/05 06:42
CRDT- 2023/02/02 00:23
PHST- 2023/01/27 00:00 [revised]
PHST- 2022/11/14 00:00 [received]
PHST- 2023/01/31 00:00 [accepted]
PHST- 2023/04/05 06:42 [medline]
PHST- 2023/02/03 06:00 [pubmed]
PHST- 2023/02/02 00:23 [entrez]
AID - 10.1111/ejh.13937 [doi]
PST - ppublish
SO  - Eur J Haematol. 2023 May;110(5):564-570. doi: 10.1111/ejh.13937. Epub 2023 Feb 
      15.