Phase 1 study of selinexor in combination with salvage chemotherapy in Adults with relapsed or refractory Acute myeloid leukemia

• Published in: Leukemia & lymphoma 2023-12, Vol.64 (13), p.2091-2100
• Main Authors: Bhatnagar, Bhavana, Zhao, Qiuhong, Mims, Alice S, Vasu, Sumithira, Behbehani, Gregory K, Larkin, Karilyn, Blachly, James S, Badawi, Mohamed A, Hill, Kasey L, Dzwigalski, Kyle R, Phelps, Mitch A, Blum, William, Klisovic, Rebecca B, Ruppert, Amy S, Ranganathan, Parvathi, Walker, Alison R, Garzon, Ramiro
• Format: Article
• Language: English
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428194.2023.2253480

Selinexor, an oral inhibitor of the nuclear transport protein Exportin-1, shows promising single-agent activity in clinical trials of relapsed/refractory (R/R) acute myeloid leukemia (AML) and preclinical synergy with topoisomerase (topo) IIα inhibitors. We conducted a phase 1, dose-escalation study of selinexor with mitoxantrone, etoposide, and cytarabine (MEC) in 23 patients aged < 60 years with R/R AML. Due to dose-limiting hyponatremia in 2 patients on dose level 2 (selinexor 40 mg/m ), the maximum tolerated dose was 30 mg/m . The most common grade ≥ 3 treatment-related non-hematologic toxicities were febrile neutropenia, catheter-related infections, diarrhea, hyponatremia, and sepsis. The overall response rate was 43% with 6 patients (26%) achieving complete remission (CR), 2 (9%) with CR with incomplete count recovery, and 2 (9%) with a morphologic leukemia-free state. Seven of 10 responders proceeded to allogeneic stem cell transplantation. The combination of selinexor with MEC is a feasibile treatment option for patients with R/R AML.