Selinexor Combo Effective For Relapsed Multiple Myeloma; Could it Benefit COVID Patients, Too?

Selinexor Could Be a “Critical New Direction” in Multiple Myeloma Treatment

• Most patients with multiple myeloma eventually relapse and become refractory to available therapies
• Selinexor, in combination with dexamethasone and bortezomib, improves survival without increasing toxicity
• This drug is also under investigation for reducing inflammation in COVID-19 patients

When treating multiple myeloma patients, you have a range of therapies at your disposal, including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. Nevertheless, most patients will eventually relapse and their cancers become unresponsive to these therapies, leaving them with limited remaining options and a poor prognosis. For these patients, the combination of selinexor plus dexamethasone represents a “critical new direction” in treatment, Dana-Farber Cancer Center medical oncologist Dr. Paul Richardson tells SurvivorNet Connect during a virtual conference.

Selinexor is the first drug to target exportin, the only known exporter of tumor suppressor proteins, which is over-expressed and leads to shorter survival in myeloma patients. In the STORM study, the selinexor-dexamethasone combination led to positive responses in multiple myeloma patients who were no longer responding to currently available treatments. The challenge was that this drug combo also had significant side effects, including anorexia, fatigue, nausea, and peripheral neuropathy.

Enter the BOSTON study, which added bortezomib to the selinexor-dexamethasone combination in a once-weekly, rather than twice-weekly dose. “We were able to demonstrate that there was a progression-free survival benefit in favor of the triplet compared to the doublet. And, very important, there was less toxicity,” Dr. Richardson says.

Selinexor’s ability to selectively inhibit nuclear transport also makes it a potential target for COVID-19. Blocking nuclear transport disrupts the virus’s ability to replicate. “RNA viruses, when they hijack tissue, use exportin to do what they do,” Dr. Richardson says. “It may well have an impact on cytokine release syndrome and can also influence viral replication. There’s strong science behind it.”

Mount Sinai hematologist-oncologist, Dr. Joshua Richter, recalls one patient who was hospitalized with a severe COVID-19 infection and rising levels of inflammation. After receiving a few doses of selinexor, “the inflammatory milieu calmed down,” he says. “We need more study, we need more information, but the rationale is there and we’ve seen a few patients absolutely benefit from it.”