RRMM: Incorporation of Selinexor into Clinical Practice

Paul G. Richardson, MD: You beautifully summarized the daratumumab-carfilzomib story, and that’s incredibly helpful for us to have. The other thing is, how do we put all this together? We’ve now got STOMP. We’ve got the success of STORM, recognizing what a challenging study and population of patients that study was helping. And then, very importantly, now we have the BOSTON data.

I wanted to start by saying that the current FDA approval for selinexor is based on the accelerated pathway, and that basically allows us to use selinexor orally with dexamethasone in the setting of triple class-refractory patients for whom immunomodulatory treatments failed them, proteasome inhibitors have failed them, and daratumumab or isatuximab-based therapy failed them. That’s obviously an exquisitely vulnerable group. What we’re hoping for is that the BOSTON study, with its prespecified end points and all those aspects, will provide a regulatory approval that will bring in the use of selinexor earlier. In that context, Cristina, do you think you’ll be bringing selinexor into practice earlier in the relapsed setting?

Cristina Gasparetto, MD: I might. You were pointing out the high-risk patients, for instance. That will be something to think about. When you have a patient relapsing aggressively with high-risk disease, it’s worth it to bring this type of combination in earlier on with a drug that clearly has a signal, even for this population of patients. We know very well that some of these combinations perform better in patients with slowly progressing myeloma, maybe with standard-risk myeloma, and we need something a bit more aggressive at times for this more aggressive relapse in patients for whom we are concerned because of the development of resistance.

I love the project that we have initiated with the alliance too, because I was thinking more about particularly targeting these high-risk myelomas. So I think so. When we talk about relapsed disease in myeloma and people are saying, “How do you sequence all these regimens,” it’s impossible to answer that. I think every patient is a little different, and we are going to need to have a treatment strategy that is different for each patient based on the type of myeloma, age, comorbidities. These are very important combinations, very effective, and may be targeting, also, some of these high-risk patients.

Paul G. Richardson, MD: I completely agree. As we think about the difference between standard and high risk, it becomes a bit more challenging, doesn’t it, if we think of it clinically?

Cristina Gasparetto, MD: Right.

Paul G. Richardson, MD: For example, if someone has had RVd [lenalidomide, bortezomib, dexamethasone]–daratumumab, for argument’s sake, up front, and had a great response and enjoyed daratumumab-based maintenance for a while and then relapses, I consider that patient—if they’re relapsing on daratumumab—high risk. They may not necessarily have the cytogenetics, but the fact that daratumumab has failed them is always a concern. In that setting, deploying selinexor with carfilzomib, pomalidomide, and dexamethasone is a rational next step.

Cristina Gasparetto, MD: Right, absolutely.

Paul G. Richardson, MD: Another fascinating point to share, and we touched on this as well, is that when you combine selinexor with pomalidomide—you summarized Dr Christine Chen’s data beautifully—these all-oral approaches are incredibly important during the COVID-19 [coronavirus disease 2019] era. We have anecdotal reports out of Mount Sinai [Center of Excellence for Multiple Myeloma] regarding combining selinexor with other drugs in COVID-19–infected myeloma patients and seeing striking clinical benefit. It’s worth sharing that there’s an ongoing randomized phase 2 study in COVID-19–infected patients, irrespective of myeloma, and that’s a very interesting concept.

Cristina Gasparetto, MD: Absolutely.

Paul G. Richardson, MD: This is 20 mg given 3 times a week. The science behind exportin inhibition being critical to viral replication and inflammation in coronavirus is striking. If this bears out—obviously we don’t know, but certainly some of the preliminary data are very promising—we may have a really remarkable platform in our myeloma patients that not only help them from a relapsed/refractory point of view but, who knows, perhaps can be helpful in other ways.

Cristina Gasparetto, MD: Absolutely. I love that you say that. Another important unmet need, pointing again to the high-risk patients and maintenance that we sometimes find a little more cumbersome, is, can we add a very low dose of selinexor for high-risk patients? We know very well that for some of these patients the durability of response is much shorter. Can we impact the myeloma using this new agent, targeting the myeloma in a different way? I love it.

Paul G. Richardson, MD: Yes, thank you. Cristina, that’s beautiful. This has been extremely informative. Thank you, Cristina, again, for an absolutely brilliant and insightful discussion.

Cristina Gasparetto, MD: Thank you.

Transcript edited for clarity.