Advancing Survival in Relapsed/Refractory Multiple Myeloma - Episode 4

RRMM: Outcomes of the BOSTON Study

July 28, 2020
Targeted Oncology

Paul G. Richardson, MD: That brings me now to the BOSTON study, which I think was one of the highlights of ASCO [the American Society of Clinical Oncology annual meeting] and certainly garnered a great deal of interest at EHA [the European Hematology Association] as well. I want to walk through the data, if I may. And then, Cristina, I’d love for you to share your comments.

The rationale was built from the preclinical observations that selinexor was highly synergistic with proteasome inhibition. And then, of course, there was very encouraging data from STOMP that showed that the combination was highly active and well tolerated with both bortezomib and carfilzomib. The rationale was very simply to bring forward a selinexor-based platform into early relapse, recognizing that this very courageous effort in the STORM study was in end-stage patients. Would we see a benefit by bringing selinexor in earlier?

This was a 1-to-3 prior lines of treatment study. It was a truly international, multicenter trial. What I particularly liked about BOSTON was it was a real-world study. We had participation strongly from Europe, Eastern Europe included, and we also had centers in India to reflect that point, as well as Asia.

As we think about BOSTON, it’s important to recognize that some of these centers were, for the first time, using selinexor. That’s a very important stress test for any novel agent. When you’re delivering it into the hands of centers that have never used it before, in a context of a pivotal approval-finding phase 3 trial, that is pretty courageous.

In the study, we also set about a very novel design. The control group was classically administered bortezomib/dexamethasone given until progression and/or intolerance. And in the same context, bortezomib was administered subcutaneously twice a week—days 1, 4, 8, and 11. In relapsed disease, the other major player in this space is carfilzomib. In any event, for this trial bortezomib was the control.

In the treatment arm, the experimental arm, the 3-drug platform was very innovative. We actually used the bortezomib on a weekly schedule, dexamethasone dosing was also less, and the selinexor was administered weekly at 100 mg. Now, these were 28-day cycles versus 3-weekly cycles. What’s important to note in the context of the study was the ability to cross over. In other words, if a patient was treated with bortezomib and dexamethasone and progressed, the patient could subsequently have selinexor added to their platform to see if they could derive clinical benefit. In the phase 3 setting, I think this is an important observation and an important strategy, particularly for allowing equipoise for patients entering any kind of randomized trial. The patients were typical of 1-to-3 priors. Again, very real-world experience.

Now, the primary outcome, of course, was very encouraging. There was a striking PFS [progression-free survival] benefit supportive of 3 drugs over 2. What was also very nice was the high response rates noted in favor of the 3 drugs versus the 2. We saw high quality response rates, and very interestingly, despite the crossover design, the trend in survival in favor of the 3 drugs over 2 was good. Now, I’d love for you to share your comments on this, Cristina, because this was something very reassuring and gratifying to see. What were your impressions of BOSTON?

Cristina Gasparetto, MD: Like you mentioned, I like the design a lot. In reality, when we design these trials, they’re very often cumbersome and difficult to translate to the community. While we are capable of supporting our patients more aggressively, in the community it is not the same. I love that the bortezomib was given once a week with the selinexor. That was important. In reality, we know that particularly in the community, in the relapsed setting bortezomib is used weekly. So it was important to have the data. Of course, we saw less peripheral neuropathy with the weekly administration, less amount of bortezomib even compared to the control arm, and it was still a very effective combination. The responses were good. Lots of patients were able to achieve a deep response…and that translated to longer progression-free survival rates, etc. I love to see that. I love to see these trial designs that we can bring to the community, to the older patients, or to the patients who are incapable of sustaining some of the complexities.

I think you see the same in 2020, tailoring therapy around your patients is becoming very important. We know about the younger patient who is capable of sustaining the quadruplet up front, maybe in the relapsed setting, but then we have the more frail patients for whom we have to come up with a regimen that’s sustainable. The selinexor given weekly, like we talked before, was more manageable. It was clear that the toxicity was less and was more manageable. I really like this study for this reason. The toxicity was less, including the peripheral neuropathy, which is a big deal for patients with the bortezomib. The peripheral neuropathy was actually one of the primary end points and was met. They had less neuropathy. I like that. I like what I saw. I think it’s a new regimen that can be used for patients who are sensitive to bortezomib, which makes sense. Selinexor shows synergism with the proteasome inhibitor. It’s a beautiful combination and I liked it. I was impressed.

Transcript edited for clarity.