Selinexor-Based Chemotherapy-Free or Low-Dose Chemotherapy Regimens in Acute Myeloid Leukemia, Myelodysplastic Syndromes: Efficacy and Safety

Introduction: Treatment of relapsed or refractory acute myeloid leukemia (R/R AML) has presented challenges for decades. Studies on selinexor in combination with various standard or intensive chemotherapy regimens for the treatment of AML have demonstrated promising results. Some patients with newly diagnosed AML, myelodysplastic syndromes (MDS), and secondary AML are not suitable for standard-dose induction chemotherapy. Considering the patients' physical conditions described above, we propose selinexor-containing regimens without chemotherapy or with low-dose chemotherapy.

Methods: The study was conducted in Tongji Hospital from March 2022 to May 2024.

Patients enrolled received the following treatment regimens：selinexor was initially dosed at 35 mg/m² orally administered in 2-week long cycles twice weekly, azacitidine 75 mg/m²/d on days 1 to 7, venetoclax was administered at 100 mg, 200 mg, and 400 mg on days 1-3, respectively, followed by 400 mg daily.

A few patients received other chemotherapy-free or low-dose chemotherapy regimens containing selinexor (combined with decitabine, homoharringtonine, bortezomib, and cytarabine, etc.) for personalized treatment.

Bone marrow assessments were performed weekly after treatment. R/R AML patients achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) in two weeks were recommended for allogeneic hematopoietic stem cell transplantation (allo-HSCT) as soon as possible. Patients achieving partial remission (PR) in two weeks after treatment were continued with selinexor treatment. The change of regimen will be considered when one of the following situations occurs: 1) the patients were non-remission (NR) in two weeks after treatment; 2) the patients mentioned above still have not achieved CR in three weeks.

Results: We included 31 patients, comprising 13 females and 18 males, with a median age of 53 years. This includes 4 patients with newly diagnosed AML, 5 patients with newly diagnosed MDS, 18 patients with R/R AML, 3 patients with secondary AML, and 1 patient with myeloid sarcoma. Twelve patients had chromosomal abnormalities, while 25 patients exhibited molecular abnormality. Before receiving the selinexor-containing treatment regimen, 11 patients underwent more than five cycles of chemotherapy.

After one cycle of treatment with the selinexor-containing regimen, 19 (61.3%) patients achieved CR/CRi, 6 (19.4%) patients achieved PR, resulting in an overall response rate (ORR) of 80.6%. Four patients who achieved PR subsequently received an additional cycle of selinexor-containing regimen, among whom three patients achieved CR. Twelve (38.7%) patients ultimately underwent allo-HSCT.

Among the 18 patients with R/R AML, 10 patients (55.5%) achieved CR/CRi, and 4 patients (22.2%) achieved PR, resulting in an ORR of 77.7%. Eight patients (44.4%) subsequently underwent transplantation. At the end of follow-up, 9 patients (50.0%) survived.

Among 13 newly diagnosed AML/MDS, secondary AML, and myeloid sarcoma patients, 9 (69.2%) achieved CR/CRi, 2(15.4%) achieved PR, with an ORR of 84.6%. Four patients (30.8%) underwent allo-HSCT.12 cases (92.3%) of patients were alive at the end of follow-up.

All patients were included in the safety assessment. Regarding hematologic toxicities, 26 patients experienced grade IV neutropenia with a median recovery time of 14 days, and 21 patients experienced grade IV thrombocytopenia with a median recovery time of 13 days. Non-hematologic toxicities were generally mild, with the majority (93.5%) being grade I-II reactions, which improved after drug intervention.

Conclusion:

In this study, selinexor-containing non-chemotherapy or low-dose chemotherapy regimens served as salvage therapy for R/R AML, demonstrating significantly higher rates of CR and ORR. These regimens offered transplant opportunities for suitable patients with manageable tolerability. In addition, selinexor-containing regimens also exhibited higher rates of CR and ORR in newly diagnosed AML/MDS, secondary AML, and myeloid sarcoma, with manageable tolerability for patients. Therefore, selinexor-containing regimens offer novel therapeutic options for these patients.

No relevant conflicts of interest to declare.

Selinexor has not yet received approval for the treatment of AML or MDS in China .Traditional chemotherapy have poor efficacy for AML or MDS patients , and we hope that the addition of Selinexor will improve survival outcomes.