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Addition of the nuclear export inhibitor selinexor to standard intensive treatment for elderly patients with acute myeloid leukemia and high risk myelodysplastic syndrome



Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65–80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1–24. In the second cycle, cytarabine 1000 mg/m2 twice daily, days 1–6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69–91%) vs. 59% (45–72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively (p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902),

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Fig. 1: Consort diagram.
Fig. 2: Overall survival and event-free survival.
Fig. 3: Hematological recovery after cycle 1.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.


  1. DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, et al. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020;383:617–29.

    CAS  Article  Google Scholar 

  2. A Study of Gilteritinib Versus Midostaurin in Combination With Induction and Consolidation Therapy Followed by One-year Maintenance in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndromes With Excess Blasts-2 With FLT3 Mutations Eligible for Intensive Chemotherapy - Full Text View - (accessed 5 Mar2022).

  3. A Study of Ivosidenib or Enasidenib in Combination With Induction Therapy and Consolidation Therapy, Followed by Maintenance Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myedysplastic Syndrome EB2, With an IDH1 or IDH2 Mutation, Respectively, Eligible for Intensive Chemotherapy - Full Text View - (accessed 5 Mar2022).

  4. Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, et al. CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia. J Clin Oncol. 2018;36:2684–92.

    CAS  Article  Google Scholar 

  5. Löwenberg B, Pabst T, Maertens J, Gradowska P, Biemond BJ, Spertini O, et al. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial. Blood Adv. 2021;5:1110–21.

    Article  Google Scholar 

  6. Janssen J, Löwenberg B, Manz M, Bargetzi M, Biemond B, Borne P, et al. Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS. Cancers 2021;13.

  7. Ranganathan P, Kashyap T, Yu X, Meng X, Lai T-H, McNeil B, et al. XPO1 Inhibition using Selinexor Synergizes with Chemotherapy in Acute Myeloid Leukemia by Targeting DNA Repair and Restoring Topoisomerase IIα to the Nucleus. Clin Cancer Res. 2016;22:6142–52.

    CAS  Article  Google Scholar 

  8. Garzon R, Savona M, Baz R, Andreeff M, Gabrail N, Gutierrez M, et al. A phase 1 clinical trial of single-agent selinexor in acute myeloid leukemia. Blood. 2017;129:3165–74.

    CAS  Article  Google Scholar 

  9. Terwijn M, van Putten WLJ, Kelder A, van der Velden VHJ, Brooimans RA, Pabst T, et al. High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study. J Clin Oncol. 2013;31:3889–97.

    Article  Google Scholar 

  10. Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–47.

    Article  Google Scholar 

  11. Juliusson G. Older patients with acute myeloid leukemia benefit from intensive chemotherapy: an update from the Swedish Acute Leukemia Registry. Clin Lymphoma Myeloma Leuk. 2011;11:S54–9.

    Article  Google Scholar 

  12. Etchin J, Montero J, Berezovskaya A, Le BT, Kentsis A, Christie AL, et al. Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against AML-initiating cells engrafted into immunosuppressed NSG mice. Leukemia. 2016;30:190–9.

    CAS  Article  Google Scholar 

  13. Sweet K, Bhatnagar B, Döhner H, Donnellan W, Frankfurt O, Heuser M, et al. A 2:1 randomized, open-label, phase II study of selinexor vs. physician’s choice in older patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2021;62:3192–203.

    CAS  Article  Google Scholar 

  14. Sweet K, Komrokji R, Padron E, Cubitt CL, Turner JG, Zhou J, et al. Phase I Clinical Trial of Selinexor in Combination with Daunorubicin and Cytarabine in Previously Untreated Poor-Risk Acute Myeloid Leukemia. Clin Cancer Res. 2020;26:54–60.

    CAS  Article  Google Scholar 

  15. Bhatnagar B, Zhao Q, Mims AS, Vasu S, Behbehani GK, Larkin K, et al. Selinexor in combination with decitabine in patients with acute myeloid leukemia: results from a phase 1 study. Leuk Lymphoma. 2020;61:387–96.

    CAS  Article  Google Scholar 

  16. Kalakonda N, Maerevoet M, Cavallo F, Follows G, Goy A, Vermaat JSP, et al. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol. 2020;7:e511–e522.

    Article  Google Scholar 

  17. Grosicki S, Simonova M, Spicka I, Pour L, Kriachok I, Gavriatopoulou M, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet. 2020;396:1563–73.

    CAS  Article  Google Scholar 

  18. Lee S, Mohan S, Knupp J, Chamoun K, Bai X, Ma X, et al. Updated overall survival of eltanexor for the treatment of patients with hypomethylating agent refractory myelodysplastic syndrome. J Clin Oncol. 2021;39:e19037–e19037.

    Article  Google Scholar 

  19. Study of the Safety, Tolerability and Efficacy of KPT-8602 in Participants With Relapsed/Refractory Cancer Indications. (accessed 6 Mar2022).

  20. Chua CC, Roberts AW, Reynolds J, Fong CY, Ting SB, Salmon JM, et al. Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT): A Phase Ib Dose-Escalation Study of Venetoclax Combined With Modified Intensive Chemotherapy. J Clin Oncol. 2020;38:3506–17.

    CAS  Article  Google Scholar 

  21. Luedtke DA, Su Y, Liu S, Edwards H, Wang Y, Lin H, et al. Inhibition of XPO1 enhances cell death induced by ABT-199 in acute myeloid leukaemia via Mcl-1. J Cell Mol Med. 2018;22:6099–111.

    CAS  Article  Google Scholar 

  22. Freeman SD, Virgo P, Couzens S, Grimwade D, Russell N, Hills RK, et al. Prognostic relevance of treatment response measured by flow cytometric residual disease detection in older patients with acute myeloid leukemia. J Clin Oncol. 2013;31:4123–31.

    Article  Google Scholar 

  23. Veltri L, Rezvani K, Oran B, Mehta R, Rondon G, Kebriaei P, et al. Allotransplants for Patients 65 Years or Older with High-Risk Acute Myeloid Leukemia. Biol Blood Marrow Transpl. 2019;25:505–14.

    Article  Google Scholar 

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The Authors thank the local and central data managers as well as the HOVON Data center Trial team and Karyopharm for free drug supply.


Dutch Cancer Foundation for financial support; Karyopharm for financial support and delivery of drug for free.

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writing—original draft preparation, JJWMJ, GO, BL and YvN. All authors have read, commented on and agreed to the published version of the manuscript.

Corresponding author

Correspondence to J. J. W. M. Janssen.

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Conflict of interest

JJWMJ: Research support: Novartis, BMS. President, Apps for Care and Science, nonprofit foundation supported by Abbvie, Alexion, Amgen, Astellas, BMS, Daiichi-Sankyo, Janssen-Cilag, Olympus, Incyte, Sanofi Genzyme, Servier, Jazz, Takeda. Honoraria: Abbvie, Novartis, Pfizer, Incyte. BL: Advisory role with honoraria for AbbVie, Astellas, Bristol Myers Squibb/Celgene, Catamaran Bio, Celgene, AvenCell/GeMoaB, Frame Pharmaceuticals, Gilead, Kronos Bio, Oxford Biomedica, Servier, holding stocks of Frame Pharmaceuticals. YC: consulting fees from MSD, Novartis, Incyte, BMS, Pfizer, Abbvie, Roche, Jazz, Gilead, Amgen, Astra-Zeneca Servier; Travel support from MSD, Roche, Gilead, Amgen, Incyte, Abbvie, Janssen, Astra-Zeneca, Jazz. GJO: Research support: Novartis, J&J, Celgene, Becton Dickinson; Consultancy: J&J, Sunesis, Celgene, Roche; Advisory board: Novartis, Pfizer, BMS, J&J, Sunesis, Celgene, Agios, Amgen, Astellas, Roche, Jazz Pharmaceuticals, Merus. Others: None declared. The funders had no role in the design of the study, nor in the collection, analyses, or interpretation of data, nor in the writing of the manuscript, or in the decision to publish the results.

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Janssen, J.J.W.M., Löwenberg, B., Manz, M. et al. Addition of the nuclear export inhibitor selinexor to standard intensive treatment for elderly patients with acute myeloid leukemia and high risk myelodysplastic syndrome. Leukemia (2022).

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