Selinexor: Rationale for Use in R/R MM Patients
Joseph Mikhael, MD, provides a brief overview of the relapsed/refractory multiple myeloma landscape and explains the mechanism of action of selinexor.
Joseph Mikhael, MD: Welcome to this CancerNetwork Between the Lines program. Today's article is entitled Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients. My name is Dr. Joseph Mikhael and I have the privilege of discussing this article with my dear friend and colleague Dr. Hakan Kaya. Thank you so much for joining me, my friend.
Hakan Kaya, MD: Thank you, Joe. It's nice to be here.
Joseph Mikhael, MD: Before I dive into the article, let's just set a little bit of background to the discussion here. There has been tremendous evolution in relapsed and refractory multiple myeloma over the last several years. In fact, we could argue more than almost any other malignancy have we seen more options emerge, and indeed better outcomes emerge as a result of it. As we've seen a trend, we're now seeing this with selinexor. The trend that we've been seeing is that agents prove themselves in multiple relapsed settings, typically as a single agent, and then move earlier in the disease course, often in combination. This article is going to highlight what we're seeing with selinexor. Selinexor is an agent that was initially approved twice weekly along with dexamethasone in the heavily relapsed setting and now we're seeing it move forward and we're going to be discussing its combination with carfilzomib shortly to remind us of selinexor is a first-in-class agent of what we call XPO1 inhibitors. Briefly what this means is we have good tumor suppressors inside the nucleus, things like P53 that we want to retain in the nucleus because that will keep the cell in check. However, in malignancy states, those are expelled out of the nucleus through a pathway called the Exportin-1 or XPO1 pathway. When that happens, the cell can become more malignant, it is less under the care of the rest of the body as it were, and it can grow and multiply. This is what we see in multiple malignancies in a particular multiple myeloma. Selinexor is an XPO1 inhibitor, so it blocks that pathway so that good tumor suppressors can remain inside the nucleus.
