BOSTON Study; SVd in Relapsed/Refractory Multiple Myeloma

Keith Stewart, MBChB: New drugs are coming out. Let’s begin with selinexor, which has been approved by the FDA, so it is available. There are recent updates from the BOSTON study with the combination of selinexor with Velcade. Does anybody who participated in that want to comment?

Nooper Raje, MD: The STORM data were what got selinexor approved. The nice thing about the BOSTON trial is that they have used bortezomib on a weekly schedule, in a subcutaneous way. It’s more of a real-world way of using bortezomib. The other thing they’ve done with the selinexor in this combination is they’ve used weekly dosing of selinexor, although at 100 mg, so that’s something we can argue about. They did see a benefit in terms of a progression-free survival of a little over 4 months. This is hopefully going to get the drug finally approved. As far as selinexor is concerned, most of us still worry about the toxicity associated with selinexor. Depending on what your partner drug is going to be, it’s important to dose-modify selinexor so that it’s well tolerated, and patients can stay on medication.

Keith Stewart, MBChB: Let’s describe selinexor, for those of you who may not be familiar with it. It’s an orally delivered agent. It has a novel target, which is exportin, a protein that shuttles things from the nucleus to the cytoplasm and back. But it can be blocked by this drug, so it’s a completely novel mechanism of action. It is approved by the FDA as a single agent in heavily pretreated patients. They were called penta-refractory, 5 prior regimens with a response rate of about 26%. In this BOSTON trial that we’ve just described, was a randomized phase 3 trial of bortezomib-dexamethasone vs bortezomib-dexamethasone and selinexor. It was mostly done in Europe, because the control arm wasn’t that attractive in the United States. But as Noopur just pointed out, there was about a 4-month progression-free survival advantage.

Peter Voorhees, MD: This was a logical way for them to get regulatory approvals in earlier relapse. Given the fact that we have other proteasome-inhibitor-based triplets that we’ve already talked about: daratumumab-carfilzomib-dexamethasone, soon to be isatuximab-carfilzomib-dexamethasone, pomalidomide-bortezomib-dexamethasone. In a similar patient population, just given the adverse-effect profile that Noopur alluded to, I don’t think we’re going to be using this a lot in this particular clinical scenario.

Keith Stewart, MBChB: Tom, what do you think? How are you going to be using it?

Thomas G. Martin, MD: We’ve reserved the use at the current time in the penta-refractory scenario where we don’t have anything left. We don’t have a clinical trial slot for a patient, and we don’t have any other therapeutic options. We have tried it, and it’s a tough drug to give. There’s no doubt about it. You have to be very diligent about checking their electrolytes, giving them fluids, giving them antinausea medicines, checking in with the patients. But you do get some patients who you wouldn’t believe you’d get a response to. It’s reasonable to try in patients, either in the combination of bortezomib-selinexor-dexamethasone, or just selinexor and dexamethasone. Give them a cycle and 4 weeks. Make sure they get through it OK. If they have a response, you can continue. But it is, in general, a lot more work than all the other regimens.

Keith Stewart, MBChB: In fairness to the drug, when it was dropped to weekly dosing, as Noopur described in the BOSTON trial, it apparently looked like it was quite a bit better tolerated, right?

Nooper Raje, MD: We’ve been participating in what’s called the STOMP trial, which has partnered selinexor with a lot of different agents. And we’ve been very impressed with 2 combinations in relapsed/refractory patients: carfilzomib with selinexor and dexamethasone. That has had a good response rate, as well as daratumumab and selinexor. We learned with other oral drugs, you get more drug in patients with lower doses. And we’ve been aggressive at cutting the doses. Then patients can stay on. As Tom said, in some of these very refractory patients, there have been some dynamite responses. We just don’t have a biomarker for it to say who’s going to be the person who responds, unfortunately. But there are some people I’ve treated who have really benefited.

Transcript edited for clarity.