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. Issue 13 (10th November 2021)

• Record Type: Journal Article
• Authors: Sweet, Kendra; Bhatnagar, Bhavana; Döhner, Hartmut; Donnellan, Will; Frankfurt, Olga; Heuser, Michael; Kota, Vamsi; Liu, Hongtao; Raffoux, Emmanuel; Roboz, Gail J.; Röllig, Christoph; Showel, Margaret M.; Strickland, Stephen A.; Vives, Susana; Tang, Shijie; Unger, Thaddeus J.; Joshi, Anita; Shen, Yao; Alvarez, Mariano J.; Califano, Andrea; Crochiere, Marsha; Landesman, Yosef; Kauffman, Michael; Shah, Jatin; Shacham, Sharon; Savona, Michael R.; Montesinos, Pau
• Is Part Of: Leukemia & lymphoma. Volume 62:Issue 13(2021)
• Page Start: 3192
• Page End: 3203
• Publication Date: 2021-11-10
• Subjects: Selinexor -- AML -- relapsed -- refractory; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.1080/10428194.2021.1950706
• Languages: English
• ISSNs: 1042-8194

Abstract

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.