December 18, 2020 - The FDA has approved selinexor in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least 1 previous therapy.
The FDA has approved selinexor (Xpovio) in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least 1 previous therapy.1
"Today's US approval broadens the existing label for [selinexor] and allows Karyopharm to offer a new, highly active, treatment option to a significantly expanded patient population," Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm, stated in a press release. "We believe the expanded reach of [selinexor] will address a critical need for patients with multiple myeloma given its novel mechanism of action, convenient oral administration and established rapid and sustained efficacy profile."
The label expansion was supported by data from the pivotal phase 3 BOSTON trial, in which the selinexor combination resulted in a statistically significant improvement in progression-free survival (PFS) vs bortezomib/dexamethasone alone in patients with multiple myeloma who had previously received 1 to 3 lines of treatment.
Updated data from the trial were reported during the 2020 ASCO Virtual Scientific Program showed that the median PFS was 13.93 months with the selinexor regimen vs 9.46 months with bortezomib/dexamethasone alone; this translated to a 30% reduction in the risk of disease progression or death (HR, 0.70; P = .0066).2 Notably the PFS benefit proved to be consistent across all subgroups analyzed, including age, high-risk cytogenetics, frailty, prior proteasome inhibitor treatment, prior receipt of lenalidomide (Revlimid), and number of previous lines of therapy.
Moreover, the triplet was also associated with a higher overall response rate (ORR) in the overall population and across patient subsets. The ORR in the total study population was 76.4% with the selinexor triplet vs 62.3% with the doublet (P = .0012). The median time to response was 1.1 months with the triplet vs 1.4 months with the doublet, and the median duration of response was 20.3 months vs 12.9 months, respectively.
In the global, randomized, open-label, controlled phase 3 BOSTON trial, investigators examined selinexor plus bortezomib and dexamethasone vs bortezomib and dexamethasone alone in patients with multiple myeloma who had received 1 to 3 previous therapies.
To be eligible for enrollment, patients had to have progressive measurable multiple myeloma per International Myeloma Working Group criteria, had to have received 1-3 previous lines of treatment for their disease, an ECOG performance status of 0-2, and acceptable hepatic and hematopoietic function. Those with moderate or severe renal impairment were permitted, but those who needed dialysis were excluded.
Participants were randomized 1:1 to receive either the triplet or the doublet. Those in the investigative arm received selinexor at 100 mg on days 1, 8, 15, 22, and 29; subcutaneous bortezomib at a dose of 1.3 mg/m2 on days 1, 8, 15, and 22; and oral dexamethasone at a dose of 20 mg on days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30. Those in the control arm received bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11, and dexamethasone at 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12.
Additional results revealed that the median time to next therapy in the investigative arm was 16.1 months vs 10.8 months in the control arm (HR, 0.66; 95% CI, 0.50-0.86; P = .0012). The median OS had not yet been reached with the selinexor regimen vs 25 months with bortezomib/dexamethasone alone (HR, 0.84; 95% CI, 0.57-1.23; P = .19).
The triplet also elicited a higher response rate across the subgroups analyzed. In those aged 65 years and older, these rates in the investigative and control arms were 76.1% vs 64.4%, respectively (P = .0243); in those with high-risk cytogenetics, these rates were 77.3% vs 55.8%, respectively (P = .0008), and in those with creatinine clearance of 30 mL/min-60 mL/min, these rates were 79.2% vs 56.7% (P = .0055).
In those who received 1 previous line of treatment, the triplet elicited an ORR of 80.8% vs 65.7% (P = .0082) in those who received the doublet; these rates were 77.6% vs 59.3% (P = .0005), respectively, in those who received prior bortezomib and 67.5% vs 53.2% (P = .0354), respectively, in those who had previously received lenalidomide.
With regard to safety, the rate of peripheral neuropathy was found to be significantly lower with the triplet vs the doublet. Overall, 32.3% of those in the investigative arm experienced peripheral neuropathy vs 47.1% of those in the control arm (P = .0010). This was the most common toxicity to result in treatment discontinuation; 4.6% of patients on the triplet discontinued due to this adverse effect vs 7.4% of those on the doublet.