Evidence map›Paper›PMID 28630120›Full record

ArticleBlood2017

Selinexor-induced thrombocytopenia results from inhibition of thrombopoietin signaling in early megakaryopoiesis.

Kellie R Machlus, Stephen K Wu, Prakrith Vijey, Thomas S Soussou, Zhi-Jian Liu, Eran Shacham, T J Unger, Trinayan Kashyap, Boris Klebanov, Martha Sola-Visner and 3 more

6 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase I
In one paragraph

Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 6 registered trials, which are not on this map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01607905 phase1completednot on this map

A Phase I Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Doses of the Selective Inhibitor of Nuclear Export/SINE Compound KPT-330 in Patients With Advanced or Metastatic Solid Tumor Malignancies

TypeinterventionalSponsorKaryopharm Therapeutics IncRan2012 to 2016Enrolled192ConditionsSolid TumorArmsSelinexor, Acetaminophen
NCT02227251 phase2active not recruitingnot on this map

A Phase 2b Open-label Study of Selinexor (KPT-330) in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

TypeinterventionalSponsorKaryopharm Therapeutics IncRan2014 to 2026Enrolled244ConditionsDiffuse Large B-cell LymphomaArmsSelinexor
NCT02343042 phase1 / phase2recruitingnot on this map

A Phase 1b/2 Study of Selinexor (KPT-330) in Combination With Backbone Treatments for Relapsed/Refractory Multiple Myeloma and Newly Diagnosed Multiple Myeloma

TypeinterventionalSponsorKaryopharm Therapeutics IncRan2015 to 2027Enrolled300ConditionsMultiple MyelomaArmsSelinexor, Dexamethasone, Lenalidomide, Pomalidomide, Bortezomib
NCT02606461 phase2 / phase3completednot on this map

A Phase 2-3, Multicenter, Randomized, Double-blind Study of Selinexor (KPT-330) Versus Placebo in Patients With Advanced Unresectable Dedifferentiated Liposarcoma (DDLS)

TypeinterventionalSponsorKaryopharm Therapeutics IncRan2016 to 2021Enrolled342ConditionsDedifferentiated LiposarcomaArmsSelinexor, Placebo
NCT03071276 phase2terminatednot on this map

A Phase I/II Study of the Selective Inhibitor of Nuclear Export Selinexor (KPT-330) in Combination With Fludarabine and Cytarabine in Patients With Refractory or Relapsed Leukemia or Myelodysplastic Syndrome

TypeinterventionalSponsorSt. Jude Children's Research HospitalRan2016 to 2019Enrolled37ConditionsAcute Myeloid Leukemia (AML)ArmsSelinexor, Fludarabine, Cytarabine, methotrexate/hydrocortisone/cytarabine
NCT03110562 phase3completednot on this map

A Phase 3 Randomized, Controlled, Open-label Study of Selinexor, Bortezomib, and Dexamethasone (SVd) Versus Bortezomib and Dexamethasone (Vd) in Patients With Relapsed or Refractory Multiple Myeloma (RRMM)

TypeinterventionalSponsorKaryopharm Therapeutics IncRan2017 to 2022Enrolled402ConditionsMultiple MyelomaArmsSelinexor, Bortezomib, Dexamethasone
3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 71 citations in OpenAlex.

  1. Trial
  2. Chemotherapy-induced thrombocytopenia: from "platelet counting" to ecological repair of the bone marrow.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Phase I Trial of Selinexor in Pediatric Recurrent/Refractory Solid and CNS Tumors (ADVL1414): A Children's Oncology Group Phase I Consortium Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
  7. A germlineScience advances · 2025
    Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Treatment of multiple myeloma with selinexor: a review.Therapeutic advances in hematology · 2024
    Review
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Kellie R MachlusDivision of Hematology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.ORCID 0000-0002-2155-1050
Stephen K WuDivision of Hematology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Prakrith VijeyDivision of Hematology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Thomas S SoussouDivision of Hematology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Zhi-Jian LiuDepartment of Pediatrics, Harvard Medical School, Boston, MA.
Eran ShachamKaryopharm Therapeutics, Newton, MA; and.
T J UngerKaryopharm Therapeutics, Newton, MA; and.
Trinayan KashyapKaryopharm Therapeutics, Newton, MA; and.
Boris KlebanovKaryopharm Therapeutics, Newton, MA; and.
Martha Sola-VisnerDepartment of Pediatrics, Harvard Medical School, Boston, MA.
Marsha CrochiereKaryopharm Therapeutics, Newton, MA; and.
Joseph E ItalianoDivision of Hematology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Yosef LandesmanKaryopharm Therapeutics, Newton, MA; and.
Karyopharm Therapeutics (United States) · USBrigham and Women's Hospital · USBoston Children's Hospital · US

Funding

Cytoskeletal Mechanisms of Platelet FormationR01HL068130 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI ITALIANO, JOSEPH E · 2001 to 2021
$8.1M
Prolonged and Severe Thrombocytopenia in NeonatesR01HL069990 · NHLBI · UNIVERSITY OF FLORIDA · PI SOLA-VISNER, MARTHA C. · 2002 to 2015
$2.8M
Molecular mechanisms of megakaryocyte differentiation and maturation during inflammationK01DK111515 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI MACHLUS, KELLIE RAE · 2016 to 2020
$793k
Identification of molecular pathways that initiate proplatelet formationF32HL118865 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI MACHLUS, KELLIE RAE · 2013 to 2016
$132k
NHLBI NIH HHS F32 HL118865NHLBI NIH HHS R01 HL068130NHLBI NIH HHS R01 HL069990NIDDK NIH HHS K01 DK111515
6 · The paper itself

Abstract

Selinexor is the first oral selective inhibitor of nuclear export compound tested for cancer treatment. Selinexor has demonstrated a safety therapy profile with broad antitumor activity against solid and hematological malignancies in phases 2 and 3 clinical trials (#NCT03071276, #NCT02343042, #NCT02227251, #NCT03110562, and #NCT02606461). Although selinexor shows promising efficacy, its primary adverse effect is high-grade thrombocytopenia. Therefore, we aimed to identify the mechanism of selinexor-induced thrombocytopenia to relieve it and improve its clinical management. We determined that selinexor causes thrombocytopenia by blocking thrombopoietin (TPO) signaling and therefore differentiation of stem cells into megakaryocytes. We then used both in vitro and in vivo models and patient samples to show that selinexor-induced thrombocytopenia is indeed reversible when TPO agonists are administered in the absence of selinexor (drug holiday). In sum, these data reveal (1) the mechanism of selinexor-induced thrombocytopenia, (2) an effective way to reverse the dose-limiting thrombocytopenia, and (3) a novel role for XPO1 in megakaryopoiesis. The improved selinexor dosing regimen described herein is crucial to help reduce thrombocytopenia in selinexor patients, allowing them to continue their course of chemotherapy and have the best chance of survival. This trial was registered at www.clinicaltrials.gov as #NCT01607905.

Indexed as

HydrazinesMegakaryocytesSignal TransductionThrombocytopeniaThrombopoiesisThrombopoietinTriazolesAnimalsApoptosisBlood PlateletsBone MarrowCell CountCell DifferentiationDose-Response Relationship, DrugFetusHumansHydrazinesselinexorThrombopoietinTriazoles

Identifiers

PMID28630120
PMCPMC5580272
OpenAlexW2680325098

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.