Selinexor 20mg tablets

This article aims to review the current application status and research advancements of selinexor in the treatment of acute myeloid leukemia (AML). Selinexor, as the first oral selective inhibitor of nuclear export protein Exportin-1 (XPO1), inhibits the abnormal nuclear export of tumor suppressor proteins by blocking XPO1, thereby restoring their activity and exerting antitumor effects. Clinical studies have shown that selinexor monotherapy or combination therapy has demonstrated good anti-leukemia effects in AML, especially in patients with relapsed/refractory AML. In addition, the combination of selinexor with other drugs, such as demethylating agents and FLT3 inhibitors, has shown synergistic antitumor effects. Although selinexor has shown potential, its resistance and adverse reactions still need further research and control. Future research directions include exploring the best medication schemes, clarifying the appropriate population, and developing new combination treatment plans to improve treatment effects and overcome drug resistance issues.

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Despite the major advancements in the repertoire for multiple myeloma (MM) treatment, this disease remains a chronically progressive plasma cell malignancy. Drug resistance and high relapse rates complicate the extended treatment strategies. However, the tumor microenvironment (TME) in MM is decisive for the success of a therapy or relapse. Aiming to improve the outcome of relapsed and refractory MM patients, Selinexor has entered the drug arsenal of myeloma therapy through the implementation of a novel therapeutic approach by selectively inhibiting the nuclear export receptor Exportin-1 (XPO1). Selinexor leads to the inactivation of cancer-related proteins and induces apoptosis by disrupting the nucleocytoplasmic flow in myeloma cells. While this drug is selectively cytotoxic to neoplastic cells, Selinexor's immunomodulatory impact on the TME is currently being investigated. The aim of this review was to elucidate Selinexor's capacity to influence the cell interaction network of the TME from an immunological perspective. Deciphering the complex interplay of highly plastic immune cells provides a contribution to the molecular-biological exploration of disease initiation and progression in MM. Unraveling the novel therapeutic targets of the immunological TME and evaluating the advanced immunotherapeutic regimens implementing Selinexor will shape the future directions of immune-oncotherapy in MM.

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Background: Selinexor, a first-in-class, oral exportin-1 inhibitor, showed activity in penta-refractory multiple myeloma (MM) in early trial exploration; however, the side-effect profile of twice-weekly dosing led to hesitant incorporation into widespread practice. Here, our objective is to provide updated clinical evidence highlighting the preserved efficacy and improved tolerability of once-weekly selinexor at lower doses in patients with previously treated MM compared to twice-weekly regimens. Methods: Patient-level data from the BOSTON, STOMP, STORM, and XPORT-MM-028 clinical trials were systematically evaluated to elucidate relationships between selinexor dosing schedule, regimen toxicities, and efficacy in patients with MM that had progressed after at least one prior therapy. Results: Updated results on once-weekly selinexor in combination with other anti-MM agents showed a reduced adverse event profile and improved tolerability compared with twice-weekly selinexor regimens, without compromise in efficacy. Furthermore, new data from several regimens with weekly selinexor delivery suggest that patients who had selinexor dose reductions or were treated in cohorts with a lower selinexor starting dose had reduced rates of adverse events, and superior durations of response. Weekly selinexor in combination with pomalidomide or carfilzomib in particular showed efficacy in difficult-to-treat, multiclass relapsed/refractory MM, including MM refractory to prior BCMA-directed therapies. Conclusions: In a rapidly evolving field of previously treated MM, lowering of selinexor dose and frequency into weekly regimens showed a more feasible and tolerable treatment with continued efficacy when compared to twice-weekly schedules, paving the path for effective management of multiclass refractory MM, including patients with very advanced disease.

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OBJECTIVE: To report long-term efficacy and safety of selinexor maintenance therapy in adults with TP53 wild-type (TP53wt) stage IV or recurrent endometrial cancer (EC) who achieved partial remission (PR) or complete remission (CR) following chemotherapy. METHODS: Analysis of the prespecified, exploratory subgroup of patients with TP53wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53wt EC and across other patient subgroups were exploratory endpoints. Safety and tolerability were also assessed. RESULTS: Of the 263 patients enrolled in the SIENDO trial, 113 patients had TP53wt EC; 70/113 (61.9%) had TP53wt/proficient mismatch repair (pMMR) EC, and 29/113 (25.7%) had TP53wt/deficient mismatch repair (dMMR) EC. As of April 1, 2024, the median PFS (mPFS) for TP53wt patients who received selinexor compared with placebo was 28.4 versus 5.2 months (36.8-month follow-up, HR 0.44; 95% CI 0.27-0.73). A benefit in mPFS was seen with selinexor versus placebo regardless of MMR status (patients with TP53wt/pMMR EC: 39.5 vs 4.9 months, HR 0.36; 95% CI 0.19-0.71; patients with TP53wt/dMMR EC: 13.1 vs 3.7 months, HR 0.49; 95% CI 0.18-1.34). Selinexor treatment was generally manageable, with no new safety signals identified. CONCLUSION: In the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931).

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NCT04562389 (ClinicalTrials.Gov).

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