Sagar Lonial, MD
Selinexor (KPT-330), a promising drug that blocks the transport of tumor-suppressor proteins out of the cell nucleus, thereby retarding cell malignancy, continues to be tested successfully as combination therapy in heavily pretreated patients with relapsed/refractory multiple myeloma (MM). The phase III BOSTON trial is enrolling patients at over 170 clinical centers across 23 countries globally, and is expecting completion of enrollment in 2018 with top-line data anticipated in 2019.
The trial is seeking to randomize 364 adult participants to receive the triplet or bortezomib and dexamethasone. The primary endpoints are progression-free survival (PFS) and ORR. Notably, patients who have progressive disease while on bortezomib and dexamethasone will have the option to cross over to the experimental arm to be treated with selinexor.
Figure. Selinexor in Relapsed/Refractory Multiple Myeloma
Unique Mechanism of Action
Selinexor inhibits chromosomal maintenance protein exportin-1 (XPO1), levels of which cancer cells increase in order to transfer tumor-suppressor proteins out of the nucleus, leading to inactivation of these cancer-fighting proteins.1,2
High levels of XPO1 also promote production of oncoproteins that fuel the growth of the tumor. Selinexor’s mechanism of blocking XPO1, limiting the production of oncoproteins, and preventing the transfer of tumor-suppressor proteins out of the nucleus has emerged as a promising strategy.
... to read the full story