General AML

Selinexor monotherapy in R/R AML patients: a phase 1 study

Selinexor is a novel, Selective Inhibitor of Nuclear Export (SINE) compound, which inhibits Exportin 1 (XPO1), a karyopherin protein, that facilitate the nuclear export of Tumor Suppressor Proteins (TSPs). In Acute Myeloid Leukemia (AML) patients, high levels of XPO1 is associated with poor outcomes.

Ramiro Garzon from The Ohio State University, USA, and colleagues published results from their phase I study (NCT01607892). In this study, the safety and efficacy of selinexor, a XPO1 inhibitor, was investigated in patients with advanced hematological malignancies including Relapsed or Refractory (R/R) AML. The results of the study were published ahead of print in Blood

Between January 2013–June 2014, ninety-five R/R AML (median age = 70) patients were enrolled. Patients received either 4, 8 or 10 doses of selinexor in 21 or 28-day cycle. The primary endpoints of the study were to determine the safety, tolerability and the Recommended Phase-2 Dose (RP2D) of selinexor. The secondary endpoints of the study were to assess tumor response and Overall Survival (OS).

The key results of the study were:
  • Common grade 1–2 Adverse Effects (AEs) in patients include fatigue (60%), anorexia (53%), nausea (53%), diarrhea (39%), vomiting (38%) and weight loss
  • Grade 3–4 AEs include thrombocytopenia (19%), anemia (15%), fatigue (14%) and neutropenia (13%)
  • RP2D was 60mg (~35 mg/m2) given twice weekly in a 4-week cycle
  • 14% of evaluable patients (11/81) achieved Objective Response (OR)
  • ≥50% decrease in Bone Marrow (BM) blasts from baseline was observed in 31% of patients (20/65) whom had post treatment BM assessment
  • Median Progression Free Survival (PFS) in patients responding to (responders) and not responding (non-responders) to selinexor; 5.1 vs 1.3 months, HR = 3.1, P = 0.008
  • Median OS in responders and non-responders; 9.7 vs 2.7 months, HR = 3.1, P = 0.01

Monotherapy with selinexor was tolerable in patients with R/R AML. Based on the findings of this phase I study, a phase II study is underway to identify “predictive biomarkers” of selinexor response in patients.


Selinexor is a novel, first-in-class, Selective Inhibitor of Nuclear Export (SINE) compound, which blocks XPO1 function, leads to nuclear accumulation of tumor suppressor proteins (TSPs) and induces cancer cell death. A phase I dose-escalation study was initiated to examine the safety and efficacy of selinexor in patients with advanced hematological malignancies. Ninety-five patients with relapsed or refractory acute myeloid leukemia (AML) were enrolled between January 2013 and June 2014 to receive 4, 8 or 10 doses of selinexor in 21- or 28-day cycle. The most frequently reported adverse events (AEs) in patients with AML were grade 1 or 2 constitutional and gastrointestinal toxicities, which were generally manageable with supportive care. The only non-hematologic, grade 3/4 AE occurring in >5% of the patient population was fatigue (14%). There were no reported DLTs or evidence of cumulative toxicity. The recommended phase 2 dose (RP2D) was established at 60mg (~35 mg/m2) given twice weekly in a 4-week cycle based on the totality of safety and efficacy data. Overall, 14% of the 81 evaluable patients achieved an objective response (OR) and 31% percent showed ≥50% decrease in bone marrow (BM) blasts from baseline. Patients achieving an OR had a significant improvement in median progression free survival (PFS) (5.1 vs 1.3 months, p=0.008, HR 3.1) and overall survival (OS) (9.7 vs 2.7 months, p=0.01, HR 3.1) compared to non-responders. These findings suggest that selinexor is safe as a monotherapy in patients with relapsed or refractory AML and have informed subsequent phase II clinical development.

  1. Garzon R. et al., A phase I clinical trial of single-agent selinexor in acute myeloid leukemia. Blood. 2017 Mar 23. DOI: 1182/blood-2016-11-750158. [Epub ahead of print].
Download this article:

You can now download this article in Adobe PDF® format.

Download as PDF