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.
Kendra SweetBhavana BhatnagarHartmut DöhnerWill DonnellanOlga FrankfurtMichael HeuserVamsi KotaHongtao LiuEmmanuel RaffouxGail J RobozChristoph RölligMargaret M ShowelStephen A StricklandSusana VivesShijie TangThaddeus J UngerAnita JoshiYao ShenMariano J AlvarezAndrea CalifanoMarsha CrochiereYosef LandesmanMichael KauffmanJatin ShahSharon ShachamMichael R SavonaPau MontesinosPublished in: Leukemia & lymphoma (2021)
Selinexor, a selective inhibitor of nuclear export, has demonstrated promising activity in patients with acute myeloid leukemia (AML). This randomized, phase II study evaluated selinexor 60 mg twice weekly (n = 118) vs. physician's choice (PC) treatment (n = 57) in patients aged ≥60 years with relapsed/refractory (R/R) AML. The primary outcome was overall survival (OS). Median OS did not differ significantly for selinexor vs. PC (3.2 vs. 5.6 months; HR = 1.18 [95% CI: 0.79-1.75]; p = 0.422). Complete remission (CR) plus CR with incomplete hematologic recovery trending in favor of selinexor occurred in a minority of patients. Selinexor treated patients had an increased incidence of adverse events. The most common grade ≥3 adverse events were thrombocytopenia, febrile neutropenia, anemia, hyponatremia. Despite well-balanced baseline characteristics, there were numerically higher rates of TP53 mutations, prior myelodysplastic syndrome, and lower absolute neutrophil counts in the selinexor group; warranting further investigation of selinexor in more carefully stratified R/R AML patients.Registered trial: NCT02088541.
Keyphrases
- acute myeloid leukemia
- end stage renal disease
- open label
- newly diagnosed
- phase ii study
- ejection fraction
- chronic kidney disease
- emergency department
- peritoneal dialysis
- clinical trial
- primary care
- acute lymphoblastic leukemia
- heart failure
- phase iii
- rheumatoid arthritis
- allogeneic hematopoietic stem cell transplantation
- physical activity
- randomized controlled trial
- double blind
- multiple myeloma
- peripheral blood