Selinexor-Based Triplet Shines in Patients With PI-Naive Myeloma

Binod Dhakal, MD, associate professor of medicine in the Division of Hematology at the Medical College of Wisconsin, discusses the survival benefit and manageable toxicity with selinexor (Xpovio), bortezomib (Velcade), and dexamethasone (SVd) in patients with proteasome inhibitor (PI)-naive multiple myeloma.

This group of patients are important to note in the updated subgroup analysis of the BOSTON trial (NCT03110562), according to Dhakal. In PI-naïve patients, SVd demonstrated a better progression-free survival (PFS) and overall survival over bortezomib and dexamethasone alone.

While the SVd arm had higher rates of cytopenia and some gastrointestinal events in PI-naïve patients, its adverse event profile was considered manageable with a once-weekly dosing schedule and supportive care, Dhakal says. With proper management, it is a relevant combination in this population of patients who may not be able to receive chimeric antigen receptor (CAR) T-cell therapy or other treatments.

TRANSCRIPTION

0:10 | When you look at this PI-naive patient population, which will be most of the patients in second line, and you just look at the subgroup in this SVd arm in the PI-naive patient population, the median PFS in those patients was 29.5 months. I think that is quite impressive. And there is, compared to the patients who are PI naive, in [bortezomib]/dexamethasone was 9.7 months, and this HR is 0.29. That is quite significant, right? So, that is very significant benefit. Similarly, for the overall survival, the HR is 0.54. So using that combination, the patients who are PI naive, where most of the patients would be in the second line, I think is something that we need to consider.

0:52 | Similarly, looking at the adverse event profile, cytopenia with thrombocytopenia slightly higher in the SVd arm, which is as expected, but otherwise there are not major, significant differences. For example, the nausea was present in 9% vs none [and] diarrhea with 6% vs 2%. But at the same time, the peripheral neuropathy was 10% in the [bortezomib] only vs 4% [with SVd]. This is, in general, the [adverse event] profile, which now we know how to better manage it compared to what we used to do with twice a week of selinexor, now we do once a week. With a lot of other supportive measures, including the strong anti-emetics, hydration, we have been able to manage it.

1:35 | I think this subgroup analysis of that PI-naive patient population is important. [We] really have to think about this, especially in patients who cannot get to CAR T or who cannot get to other available agents.