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

Publication

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

Journal Paper/Review - Jul 22, 2022

Janssen J J W M, Löwenberg Bob, Manz M, Biemond B J, Westerweel P E, Klein S K, Fehr M, Sinnige H A M, Efthymiou Anna, Legdeur M C J C, Pabst T, Gregor M, van der Poel M W M, Deeren Dries, Tick L W, Jongen-Lavrencic Mojca, van Obbergh F, Boersma R S, de Weerdt Okke, Chalandon Yves, Heim D, Spertini Olivier, van Sluis G, Graux Carlos, Stüssi G, van Norden Y, Ossenkoppele G J

Citation

Janssen J, Löwenberg B, Manz M, Biemond B, Westerweel P, Klein S, Fehr M, Sinnige H, Efthymiou A, Legdeur M, Pabst T, Gregor M, van der Poel M, Deeren D, Tick L, Jongen-Lavrencic M, van Obbergh F, Boersma R, de Weerdt O, Chalandon Y, Heim D, Spertini O, van Sluis G, Graux C, Stüssi G, van Norden Y, Ossenkoppele G. 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; 36:2189-2195.

Type

Journal Paper/Review (English)

Journal

Leukemia 2022; 36

Publication Date

Jul 22, 2022

Issn Electronic

1476-5551

Pages

2189-2195

Brief description/objective

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/m 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 ).