In June 2019, the U.S. FDA approved selinexor (Xpovio) in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. Myeloma patients had to have been treated with at least four prior therapies. In November 2020, the results of the BOSTON study were published which demonstrated the benefits of using selinexor earlier in the treatment pathway. The study outcomes led the U.S. FDA to approve selinexor for adults with multiple myeloma who have had at least one prior type of treatment. In the BOSTON trial patients that received treatment once-a-week with the combination of selinexor, bortezomib and dexamethasone had a 47% improvement in progression-free survival compared to twice-a-week bortezomib and dexamethasone.
Selinexor works by inhibiting the activity of exportin 1 or XPO1 in a cell. XPO1 is responsible for exporting our own natural tumour suppressors out of our cell nucleus. The cell nucleus is where our genetic information is stored. Once the suppressors are outside the cell nucleus, they are no longer effective in preventing cell growth. By selinexor inhibiting the protein XPO1, more tumour suppressors are able to stay in the nucleus and work effectively to prevent tumour growth.
It is exciting to see so many novel treatments to prevent tumour growth being explored. A company press release indicted that they have submitted a dossier to the Australian Therapeutic Goods Administration to gain approval for treatment in both multiple myeloma and diffuse large B-cell lymphoma. Approvals in Australia tend to take approximately 18 months so it will be a little while before we see this treatment available.