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Add-On Selinexor Improves PFS in Pretreated Myeloma

Adding the XPO1 inhibitor selinexor (Xpovio) to bortezomib (Velcade) plus dexamethasone reduced the risk of disease progression or death in patients with previously treated multiple myeloma, according to findings from the phase III BOSTON trial.

Among over 400 patients with one to three prior lines of therapy, median progression-free survival (PFS) improved from 9.5 months with bortezomib plus dexamethasone to 14.0 months with the addition of selinexor (HR 0.70, P=0.0066), manufacturer Karyopharm announced.

Importantly, they noted that there was no imbalance in deaths between the two study arms, and no new safety signals in the selinexor arm were identified.

The findings lend support to the FDA’s accelerated approval of selinexor last summer, which came despite the Oncologic Drugs Advisory Committee (ODAC) recommending in an 8-5 vote that the agency hold off on the quick approval, and wait until the BOSTON trial’s PFS results arrived (the primary endpoint) to confirm the drug’s benefit. ODAC members had concerns over both the drug’s activity and safety.

Karyopharm said it plans to submit these data for a second-line indication and to serve as the confirmatory trial for its accelerated approval, which was based on results of STORM Part 2, a single-arm phase II trial.

STORM Part 2 included 122 triple-class refractory myeloma patients (i.e., those who had failed a proteasome inhibitor, immunomodulatory agent, and an anti-CD38 monoclonal antibody) who were treated with selinexor plus low-dose dexamethasone at doses of 80 mg and 20 mg, respectively. All had been exposed to five different anti-myeloma drugs.

In the FDA’s approval, the agency narrowed the indication to only include patients not just exposed to but refractory to the five different agents — at least two proteasome inhibitors, two immunomodulatory agents, plus an anti-CD38 monoclonal antibody. Among the 83 patients with this so-called penta-refractory disease in STORM Part 2, a quarter had an objective response to the combination and 37% had a “minimal response” or better.

Of note, dosages for both dexamethasone and selinexor were different in BOSTON. The phase III trial randomized 402 patients to once-weekly 100-mg selinexor plus bortezomib (1.3 mg/m2) and 40-mg dexamethasone, or to standard twice-weekly bortezomib plus dexamethasone.