TY - JOUR
T1 - Addition of the nuclear export inhibitor selinexor to standard intensive treatment for elderly patients with acute myeloid leukemia and high risk myelodysplastic syndrome
AU - Janssen, J. J. W. M.
AU - Löwenberg, B.
AU - Manz, M.
AU - Biemond, B. J.
AU - Westerweel, P. E.
AU - Klein, S. K.
AU - Fehr, M.
AU - Sinnige, H. A. M.
AU - Efthymiou, A.
AU - Legdeur, M. C. J. C.
AU - Pabst, T.
AU - Gregor, M.
AU - van der Poel, M. W. M.
AU - Deeren, D.
AU - Tick, L. W.
AU - Jongen-Lavrencic, M.
AU - van Obbergh, F.
AU - Boersma, R. S.
AU - de Weerdt, O.
AU - Chalandon, Y.
AU - Heim, D.
AU - Spertini, O.
AU - van Sluis, G.
AU - Graux, C.
AU - Stüssi, G.
AU - van Norden, Y.
AU - Ossenkoppele, G. J.
N1 - Funding Information: The Authors thank the local and central data managers as well as the HOVON Data center Trial team and Karyopharm for free drug supply. Funding Information: 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. Funding Information: Dutch Cancer Foundation for financial support; Karyopharm for financial support and delivery of drug for free. Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/9
Y1 - 2022/9
N2 - 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), www.trialregister.nl).
AB - 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), www.trialregister.nl).
UR - http://www.scopus.com/inward/record.url?scp=85134692962&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41375-022-01657-3
DO - https://doi.org/10.1038/s41375-022-01657-3
M3 - Article
C2 - 35869267
SN - 0887-6924
VL - 36
SP - 2189
EP - 2195
JO - Leukemia
JF - Leukemia
IS - 9
ER -