PMID- 35379237
OWN - NLM
STAT- MEDLINE
DCOM- 20220406
LR  - 20220613
IS  - 1741-7015 (Electronic)
IS  - 1741-7015 (Linking)
VI  - 20
IP  - 1
DP  - 2022 Apr 5
TI  - Selinexor plus low-dose dexamethasone in Chinese patients with 
      relapsed/refractory multiple myeloma previously treated with an immunomodulatory 
      agent and a proteasome inhibitor (MARCH): a phase II, single-arm study.
PG  - 108
LID - 10.1186/s12916-022-02305-4 [doi]
LID - 108
AB  - BACKGROUND: Selinexor 80 mg combined with low-dose dexamethasone (Sd) 
      demonstrated significant clinical benefit in patients with relapsed/refractory 
      multiple myeloma (RRMM) who had disease refractory to a proteasome inhibitor 
      (PI), an immunomodulator (IMiD), and an anti-CD38 monoclonal antibody based on a 
      global phase II STORM study. The present study, MARCH, addresses China regulatory 
      needs to further validate the data from STORM in Chinese patients with RRMM. 
      METHODS: The MARCH study was conducted at 17 sites in China, where eligible 
      Chinese RRMM patients who had disease refractory to PI and IMiD were enrolled. 
      Selinexor 80 mg combined with dexamethasone 20 mg was administered orally on day 
      1 and day 3 of each week in 4-week cycles. The primary endpoint was the overall 
      response rate (ORR) per an independent review committee, with the null hypothesis 
      of </=15%. Patients who received at least 1 dose of study treatment were included 
      in the safety population. The pharmacokinetic (PK) profile was characterized by 
      parameter and ethnicity sensitivity analyses. RESULTS: A total of 82 patients 
      with RRMM were enrolled in the study, with a median age of 60 years. Of the 82 
      patients, 55 patients (67.1%) had high-risk cytogenetic abnormalities, defined as 
      one or more of del 17p13, t(4;14), t(14;16), or 1q amplification identified by 
      fluorescence in situ hybridization (FISH); 18 patients (22.0%) had abnormal renal 
      function. Enrolled patients were heavily pre-treated with a median prior regimen 
      number of 5. All 82 patients (100%) were refractory to both PI and IMiD, 
      including 20 patients (24.4%) categorized as triple-class refractory population 
      (refractory to PI, IMiD, and daratumumab). Ten patients (12.2%) had undergone 
      CAR-T therapy. ORR was 29.3% (95% CI 19.7, 40.4) with a median DOR of 4.7 months. 
      The median PFS and OS were 3.7 and 13.2 months, respectively. ORR was 25.0% (95% 
      CI 8.7, 49.1) in the triple-class refractory population. Efficacy was consistent 
      across various subgroups. The most frequent grade 3/4 adverse events (AEs) 
      included anemia (57.3%), thrombocytopenia (51.2%), lymphopenia (42.7%), 
      neutropenia (40.2%), hyponatremia (29.3%), and lung infection (26.8%). Serious 
      AEs were reported in 54.9% of patients. No significant drug accumulation was 
      shown following multiple administrations. No human PK ethnicity difference was 
      identified between Chinese and western patients. CONCLUSIONS: With an encouraging 
      ORR, the MARCH study has demonstrated that selinexor combined with low-dose 
      dexamethasone (Sd) delivers meaningful clinical benefit to Chinese patients with 
      RRMM, including triple-class refractory patients. AEs were expected and 
      manageable with supportive care and dose modification. TRIAL REGISTRATION: 
      ClinicalTrials.gov, NCT03944057 (May 09, 2019); Chinadrugtrials.org.cn , 
      CTR20190858 (June 05, 2019).
CI  - (c) 2022. The Author(s).
FAU - Qiu, Lugui
AU  - Qiu L
AD  - National Clinical Research Center for Blood Diseases, State Key Laboratory of 
      Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, 
      Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 
      300020, China. qiulg@ihcams.ac.cn.
FAU - Xia, Zhongjun
AU  - Xia Z
AD  - Department of Hematology, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Fu, Chengcheng
AU  - Fu C
AD  - The First Affiliated Hospital of Soochow University, Suzhou, China.
FAU - Chen, Wenming
AU  - Chen W
AD  - Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, 
      Beijing, China.
FAU - Chang, Chunkang
AU  - Chang C
AD  - Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's 
      Hospital, Shanghai, China.
FAU - Fang, Baijun
AU  - Fang B
AD  - Department of Hematology, Henan Institute of Hematology, Henan Cancer Hospital, 
      The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
FAU - An, Gang
AU  - An G
AD  - National Clinical Research Center for Blood Diseases, State Key Laboratory of 
      Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, 
      Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 
      300020, China.
FAU - Wei, Yongqiang
AU  - Wei Y
AD  - Department of Hematology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Cai, Zhen
AU  - Cai Z
AD  - Bone Marrow Transplantation Center, Department of Hematology, The First 
      Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Gao, Sujun
AU  - Gao S
AD  - Department of Hematology, the First Affiliated Hospital of Jilin University, 
      Changchun, China.
FAU - Weng, Jianyu
AU  - Weng J
AD  - Department of Hematology, Guangdong Provincial People's Hospital, Guangzhou, 
      China.
FAU - Chen, Lijuan
AU  - Chen L
AD  - Department of Hematology, Jiangsu Province Hospital, The First Affiliated 
      Hospital with Nanjing Medical University, Nanjing, China.
FAU - Jing, Hongmei
AU  - Jing H
AD  - Department of Hematology and Lymphoma Research Center, Peking University Third 
      Hospital, Beijing, China.
FAU - Li, Fei
AU  - Li F
AD  - Department of Hematology, the First Affiliated Hospital of Nanchang University, 
      Nanchang, China.
FAU - Liu, Zhuogang
AU  - Liu Z
AD  - Department of Hematology, Shengjing Hospital of China Medical University, 
      Shenyang, China.
FAU - Chen, Xiequn
AU  - Chen X
AD  - Department of Hematology, Xi Jing Hospital affiliated to the Fourth Military 
      Medical University, Xi'an, China.
FAU - Liu, Jing
AU  - Liu J
AD  - Department of Hematology, the Third Xiangya Hospital of Central South University, 
      Changsha, China.
FAU - Wang, Aihua
AU  - Wang A
AD  - Antengene Corporation Co., Ltd, Shanghai, China.
FAU - Yu, Yang
AU  - Yu Y
AD  - Antengene Corporation Co., Ltd, Shanghai, China.
FAU - Xiang, Wenxi
AU  - Xiang W
AD  - Antengene Corporation Co., Ltd, Shanghai, China.
FAU - Lynch, Kevin
AU  - Lynch K
AD  - Antengene Corporation Co., Ltd, Shanghai, China.
FAU - Yu, Zhinuan
AU  - Yu Z
AD  - Antengene Corporation Co., Ltd, Shanghai, China.
FAU - Fu, Weijun
AU  - Fu W
AD  - Department of Hematology, Changzheng Hospital, Shanghai, 200003, China. 
      fuweijun@smmu.edu.cn.
AD  - Department of Hematology, Shanghai Fourth People's Hospital, School of Medicine, 
      Tongji University, Shanghai, 200434, China. fuweijun@smmu.edu.cn.
LA  - eng
SI  - ClinicalTrials.gov/NCT03944057
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220405
PL  - England
TA  - BMC Med
JT  - BMC medicine
JID - 101190723
RN  - 0 (Hydrazines)
RN  - 0 (Immunologic Factors)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (Triazoles)
RN  - 31TZ62FO8F (selinexor)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Dexamethasone/therapeutic use
MH  - Humans
MH  - Hydrazines
MH  - Immunologic Factors/therapeutic use
MH  - In Situ Hybridization, Fluorescence
MH  - *Multiple Myeloma/chemically induced/drug therapy
MH  - *Proteasome Inhibitors/therapeutic use
MH  - Triazoles
PMC - PMC8981703
OTO - NOTNLM
OT  - Chinese patients
OT  - Multiple myeloma
OT  - Relapsed and refractory
OT  - Selinexor
COIS- YY, WX, ZY, AW, and KL are employees of Antengene Corporation Co., Ltd. The other 
      authors declare that they have no known competing financial or other interests 
      that could have appeared to influence the work reported in this paper.
EDAT- 2022/04/06 06:00
MHDA- 2022/04/07 06:00
PMCR- 2022/04/05
CRDT- 2022/04/05 05:27
PHST- 2021/12/23 00:00 [received]
PHST- 2022/02/18 00:00 [accepted]
PHST- 2022/04/05 05:27 [entrez]
PHST- 2022/04/06 06:00 [pubmed]
PHST- 2022/04/07 06:00 [medline]
PHST- 2022/04/05 00:00 [pmc-release]
AID - 10.1186/s12916-022-02305-4 [pii]
AID - 2305 [pii]
AID - 10.1186/s12916-022-02305-4 [doi]
PST - epublish
SO  - BMC Med. 2022 Apr 5;20(1):108. doi: 10.1186/s12916-022-02305-4.