Analysis of the BOSTON Trial

EP: 1.Risk of Myeloma Relapse After Frontline Therapy

EP: 2.Newly Approved Regimens for Relapsed/Refractory Multiple Myeloma

EP: 3.Clinical Data for Selinexor Use in Myeloma

EP: 4.Evolving Treatment Options for Relapsed/Refractory Multiple Myeloma

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EP: 5.Analysis of the BOSTON Trial

EP: 6.Selecting Appropriate Therapy for Patients With Relapsed/Refractory Multiple Myeloma

EP: 7.Considering Patient-, Treatment-, and Disease-Related Factors in Myeloma

EP: 8.What’s Coming Next in Relapsed/Refractory Multiple Myeloma

Joshua Richter, MD: One of the things we touched on briefly and that I was hoping we could spend a little time on is the BOSTON study, which received approval at the end of 2020. It used the selinexor–Velcade [bortezomib]–dexamethasone regimen, and I was wondering if you could give us a little granularity about the study and big takeaway points.

James Hoffman, MD: We talked about some of this earlier, but let’s dive a little deeper. Selinexor has been a topic of a lot of conversation. With the initial data, there was a lot of back and forth about the role of the drug and its approval. Once we got approval, there was a quick pivot to use it because there was a realization that it would be tough to give on the twice-a-week schedule that you referenced earlier. The BOSTON trial provides a template to use this drug in a way that’s effective, and a subset of patients will get some meaningful benefit. Another nice thing is that it seems you’ll know quickly who’s going to benefit and who’s not, so you don’t have to drag people through a lot of treatment to know who’s going to benefit.

Based on the mechanism of action, there are certainly going to be other partners who are explored, and that may offer some additional potential. The way this evolved with this drug and its approval and pivoting to this different dose and schedule is unique. But for patients who’ve failed the IMiD [immunomodulatory imide drug] class, carfilzomib-daratumumab, and maybe even 1 of the other drugs that we’ve mentioned up to this point—like belantamab and some alkylators—there aren’t a lot of drugs that can induce remissions. Here you have a drug that in this combination is not very onerous to give. I’m appreciative that I have it, and I certainly use it in this group of patients. How about yourself?

Joshua Richter, MD: There are a couple of arenas that selinexor has the ability to shine. One thing we’ve learned from the STORM study and some patients on the STOMP study is that there’s activity of selinexor in patients who have progressed beyond CAR [chimeric antigen receptor] T-cell therapies. Although most myeloma centers like ours [the Tisch Cancer Institute at Mount Sinai], and other people I’ve spoken to haven’t yet given the commercial Abecma [idecabtagene vicleucel], we’re certainly going to in the coming months. Unfortunately, those people will eventually relapse, so it’s nice to know there are some data out there about drugs that work post CAR T.

In terms of using it earlier, it’s a more select group of patients. One of the nice things that was in the final publication in The Lancet and that was presented last year at ASCO [American Society of Clinical Oncology Annual Meeting] is some of the subset analysis from the BOSTON trial, looking at patients who are older, with some renal dysfunction and high-risk cytogenetics. That’s the grouping of patients we see in clinic, and there was an advantage there of the triplet. One of the big things for me, a lot of these studies have shown us and as you pointed out perfectly, is that 100 mg is too much. Maybe a person needs 80 or 60 mg. But we’ve all moved into this realm in which it’s better to give a dose-adjusted triplet than a full-dose doublet in an older, frailer patient to get those multiple mechanisms of action. Especially for people with high-risk disease, we give a selinexor-like drug. The other thing is for people who have lymphoma-like disease, there’s a good role because selinexor also has FDA approval in diffuse large B-cell lymphoma.

James Hoffman, MD: That’s a good point. For those watching this, there’s plenty you can read about some of the discussions related to this trial and the control grouping Velcade [bortezomib]–dexamethasone and what kind of bar that was to hurdle in patients that previously received Velcade [bortezomib]. I would say that there’s not much controversy. This dose in schedule is reasonable. It’s doable, and there’s a subset of patients—some of our sickest and most difficult to treat—that can have meaningful benefit. I certainly place it firmly in the group of usable drugs. I’m happy that we have it. You’ll get a somewhat wider array of opinions about how eagerly you reach for it from the cupboard, so to speak, and where you place it in order. As we get more information and time goes by and we incorporate CAR T, some of that will get sorted out easier.

Another thing that you brought up a couple of times is that there has been a real lead on this is in terms of managing the adverse effects and monitoring patients on selinexor with Velcade [bortezomib]. You mentioned the supportive care medicines that you use, and some of these patients are coming weekly for the Velcade [bortezomib]. Is there anything else that you do in terms of monitoring these patients or informing patients before they start?

Joshua Richter, MD: Absolutely. Apart from the GI [gastrointestinal] issues, there are 2 other things we try to keep on top of. One is that there’s some hyponatremia that we see with the drug. Most of it isn’t hugely clinically significant, but patients often come in with a sodium of 129, 128 mEq/L. We tell them to keep a bag of chips on hand. This way they can have a nice salt-heavy diet if we need to make that up. The other thing is that it can suppress your counts. More specifically, selinexor has a tropism for the megakaryocytes. One of the things we’re seeing—we see this more with the late-stage selinexor usage as opposed to early relapse usage—is thrombocytopenia. If you reach for it in the first 1 to 3 lines, you’re not going to have this as much. But if you use it the way we mostly use it toward the end of the road, patients seem to get hit hard platelet-wise, and we’ve really embraced the usage of TPO [thyroid peroxidase] mimetics for those advanced patients who have burned-out marrows or have heavy marrow burden. Mostly using romiplostim, if you look at the Epocrates guidelines, you start at 1 µg/kg and week by week ramp up to a max dose of 10 µg/kg. We’ve escalated quickly in some of these patients, giving them 5 µg/kg in 1 week and 10 µg/kg the next week to keep the platelets up, so we can keep them on schedule with drug and get them over the hump. Do you have any other tips to add?

James Hoffman, MD: No. That sounds great. I know we use some romiplostim even in patients on the STORM study. That’s good advice with a rapid ramp-up. That’s something I haven’t done, but it’s reasonable. I probably will start to do that after this discussion.

Transcript Edited for Clarity