Molecular response patterns in relapsed/refractory AML patients treated with selinexor and chemotherapy

Abstract

Relapse in patients with acute myeloid leukemia (AML) is common and is associated with a dismal prognosis. Treatment options are limited and the understanding of molecular response patterns is still challenging. We analyzed the clonal response patterns of 15 patients with relapsed/refractory AML treated with selinexor in a phase II trial (SAIL). DNA was analyzed at three time points and showed a decline of mutated alleles in FLT3, SF3B1, and TP53 under SAIL treatment. Overall survival (OS) was similar between patients with declining versus persisting clones. We show an interesting long-term course of a patient who relapsed after allogeneic stem cell transplantation (alloHCT) with SF3B1- and SRSF2-mutated AML and received selinexor as maintenance treatment for 4 years. Measurable residual disease (MRD) remained detectable for 2 weeks after donor lymphocyte infusion (DLI) in this patient and then remained negative under selinexor maintenance treatment. Selinexor was tolerated well and was stopped after 4 years of SAIL treatment. We present an exploratory study and identify subclonal patterns of patients treated with selinexor.

Keywords: AML; Molecular patterns; Relapse; Selinexor.

Fig. 1

Frequency of genes that were found mutated at the time of SAIL screening and association with CR/CRi

Fig. 2

Molecular course of long-term patient under selinexor maintenance treatment. The x-axis marks the years after diagnosis. The orange and blue lines show the SRSF2 and SF3B1 MRD courses, respectively. The filled squares represent MRD positivity above the LOD of VAF 0.02% and the empty squares represent MRD negativity. Selinexor maintenance treatment started 26 days after DLI