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 Sweet, Bhavana Bhatnagar, Hartmut Döhner, Will Donnellan, Olga Frankfurt, Michael Heuser, Vamsi Kota, Hongtao Liu, Emmanuel Raffoux, Gail J. Roboz, Christoph Röllig, Margaret M. Showel, Stephen A. Strickland, Susana Vives, Shijie Tang, Thaddeus J. Unger, Anita Joshi, Yao Shen, Mariano J. Alvarez, Andrea Califano, Marsha Crochiere, Yosef Landesman, Michael Kauffman, Jatin J. Shah, Sharon Shacham, Michael R. Savona, Pau Montesinos
Abstract
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.