ASH 2020 | BOSTON study: results and R/R MM patient implications
Paul Richardson, MD, Dana-Farber Cancer Institute, Boston, MA, discusses results from the BOSTON study (NCT03110562); a phase III investigation into the combination of once-weekly selinexor with bortezomib and dexamethasone in patients with relapsed/refractory (R/R) multiple myeloma (MM). The use of selinexor, a first-in-class selective inhibitor of nuclear export (SINE), substantially increases clinical benefit while reducing neurotoxicity. The implications of this combinatorial therapy in patients is very exciting. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.
Transcript (edited for clarity)
This was very much a real world effort designed to compare in patients who received one to three prior lines of therapy, the benefit, or not, of the addition of selinexor to the bortezomib backbone. Importantly, in the three drug arm, we gave the bortezomib just weekly and we also reduce the dexamethasone dosing. So this was quite a risky strategy, one could argue, because at the end of the day, the experimental arm delivered significantly less bortezomib, significantly less dexamethasone, and the key difference was the addition of weekly selinexor which was given at a lower dose than is typically used, at 80 milligrams once a week...
This was very much a real world effort designed to compare in patients who received one to three prior lines of therapy, the benefit, or not, of the addition of selinexor to the bortezomib backbone. Importantly, in the three drug arm, we gave the bortezomib just weekly and we also reduce the dexamethasone dosing. So this was quite a risky strategy, one could argue, because at the end of the day, the experimental arm delivered significantly less bortezomib, significantly less dexamethasone, and the key difference was the addition of weekly selinexor which was given at a lower dose than is typically used, at 80 milligrams once a week. Typically, in the approved prescription, it’s 80 milligrams twice a week, and in this case, we dosed at 80 milligrams once a week based, again, on promising data from the STORM study.
Now, the exciting results of this were that, in fact, not only was the combination well-tolerated generally with some side effects that, again, proved manageable, but most importantly, a progression-free survival difference was seen in favor of the three drugs over the two and the median gain was around four and a half months across the study overall, and particularly in high-risk patients, clinical benefit was seen. What was also striking … and this was a large trial … was that neurotoxicity was substantially less in the three-drug arm. This was an a priori, secondary end point of the trial. The hypothesis was that not only would this reduction in the frequency of administration of bortezomib contribute to reduce neurotoxicity, but also, most importantly, there may be some anti-inflammatory properties to selinexor that contribute to reduction of neurotoxicity.
We’re very encouraged to see that overall there was about a halving of the rates of neuropathy and importantly, in the high grade neurotoxicities, grade three, four patients … which fortunately were few, but what we saw was that this was actually reduced by 50%. So this is a very encouraging result, in our opinion, and very promising as we go forward.
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