The National Comprehensive Cancer Network (NCCN) has added 3 different selinexor-containing regimens to its list of therapies recommended for use in patients with previously treated multiple myeloma.
The 3 newly added regimens, selinexor/bortezomib/dexamethasone (administered once weekly; SVd); selinexor/daratumumab/dexamethasone (SDd); and selinexor/pomalidomide/dexamethasone (SPd), which is an all-oral triplet therapy, have been included in the NCCN’s updated clinical practice guidelines for multiple myeloma.1
Notably, none of the 3 combinations is on the list of preferred regimens. SVd expands the NCCN’s “other recommended regimens” treatment category, and SDd and SPd, the “useful in certain circumstances” category.
The selinexor regimens were added based on data from the randomized phase 3 BOSTON trial (ClinicalTrials.gov identifier: NCT03110562), published in The Lancet in November 2020.2 The study compared SVd with combination bortezomib and dexamethasone.
“That trial showed that adding selinexor to bortezomib and dexamethasone not only improved the depth of response, but also gave more durable responses,” said Shaji Kumar, MD, chair of the NCCN guidelines panel for multiple myeloma. “It’s a regimen that can certainly be used in patients with advanced myeloma.”
Selinexor is a first-in-class selective inhibitor of nuclear export (SINE) that blocks exportin 1 (XPO1), an oncoprotein that is overexpressed in multiple myeloma cancer cells. Selinexor binds to the Cys528 residue in the cargo-binding pocket of XPO1, enabling the activation of tumor suppressor proteins to induce cell death.2
“It’s very important in cancer to switch mechanisms,” said Michael Kaufmann, MD, PhD, founder and CEO of Karyopharm, selinexor’s developer. Despite multiple myeloma’s status as an “incurable” disease, patients can live many years after diagnosis and will typically cycle through many different drugs due to relapse/refractory disease. Although multiple myeloma will eventually progress, each new drug can potentially add another 1 to 3 years of survival.
The long therapeutic course associated with the management of multiple myeloma means that fostering flexibility is of paramount importance to selecting treatment interventions, explained Kaufmann. “You want to allow [the] physician to pick the best regimen for that particular patient,” Kauffman said.
SVd is a once-weekly treatment that reduces the amount of time patients spend receiving therapy and traveling to appointments. In cases when bortezomib should not be used, SPd and SDd provide alternative options, particularly for patients who have previously been treated with pomalidomide or daratumumab.