Selinexor and Multiple Myeloma

There are various treatment options for patients with multiple myeloma (MM), including autologous hematopoietic stem cell transplantation (HSCT), thalidomide, lenalidomide, bortezomib, and daratumumab. Each patient with MM is obviously not a candidate for all of these treatments, and each treatment plan needs to be tailored for the individual patient. A consistent challenge facing both health care practitioners and patients is that none of the current medication options are curative, therefore, refractory disease is inevitable.1 However, there are new agents being developed for use in patients with MM that seek to improve outcomes in refractory disease.

One of these new agents with developing clinical trial data is a first-in-class, selective inhibitor of exportin-1 (XPO1).2 XPO1 is a protein found within the nucleus of the cell and is responsible for the transport of molecules such as tumor suppressor proteins and other oncoproteins from the nucleus to the cytoplasm.3

Increased levels of XPO1 are associated with disease progression from monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM.4 These changes may eventually translate into worse outcomes in patients with MM. Early preclinical and clinical data have shown that selinexor has activity in multiple hematologic malignancies, most notably in MM. Selinexor has been studied alone as well as in conjunction with additional agents such as dexamethasone and proteasome inhibitors.2

Based on early promising data, Vogl and colleagues published a larger phase 2 study evaluating selinexor in combination with dexamethasone in patients with MM that is refractory to current therapies.2 This was a multicenter, open-label study that evaluated selinexor 80 mg and dexamethasone 20 mg, both by mouth twice daily, in patients with MM who were refractory to lenalidomide, pomalidomide, bortezomib, carfilzomib, and anti-CD38 antibodies (daratumumab or isatuximab). The primary end point was overall response rate (ORR) which included a partial response or better (characterized as a very good partial response or complete response) and was determined by an independent review group  using modified International Myeloma Working Group (IMWG) criteria.5

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