Selinexor combination ‘extremely effective’ in relapsed, refractory myeloma
Once weekly selinexor, carfilzomib and dexamethasone showed an overall response rate of 72% in patients with relapsed/refractory multiple myeloma who have received a median of four lines of prior therapy, according to data presented at ASCO20 Virtual Scientific Program.
In this phase 1b/2 study, Cristina Gasparetto, MD, associate professor of medicine at Duke University Medical Center, and colleagues examined the maximum tolerated dose, recommended phase 2 dose, efficacy and safety of once weekly treatment with selinexor (Xpovio, Karyopharm Therapeutics) and dexamethasone plus carfilzomib (Kyprolis, Amgen) in carfilzomib-naive patients with relapsed multiple myeloma.
Patients received oral selinexor dosed once weekly at 80 mg or 100 mg; carfilzomib dosed once weekly (on days 1, 8 and 15 of 28-day cycle) at 56 mg/m2 or 70 mg/m2; and dexamethasone dosed once weekly at 40 mg, according to the abstract. Of 18 enrolled patients, 50% and 56% were refractory to bortezomib (Velcade, Takeda) and lenalidomide (Revlimid, Celgene), 50% received prior pomalidomide treatment (of these, 44% were refractory) and 61% received prior daratumumab (Darzalex, Janssen) treatment (of these, 50% were refractory).
Gasparetto and colleagues reported that the maximum tolerated dose was 80 mg of once weekly selinexor, 56 mg/m2 of once weekly carfilzomib and 40 mg of once weekly dexamethasone.
Seventy-two percent of patients achieved ORR and 79% of patients achieved CBR, with four patients achieving complete responses, seven very good partial responses, two partial responses and one minimal response. Further, researchers observed stable disease in three patients.
“We had more than 50% of patients with prior exposure and failure to daratumumab and the responses of these patients were identical the entire cohort of patients,” Gasparetto told Healio. This was a very important arm for us because many patients receive daratumumab in the upfront setting on the first relapse. When they fail the daratumumab, we struggle to determine which one is going to be the best combination and some of these patients, unfortunately, don’t do well after relapsing after daratumumab.”
The researchers also reported that the combination was well tolerated with no new safety signal. Common treatment-related adverse events included thrombocytopenia, nausea, anemia, fatigue, anorexia, weight loss and neutropenia. The side effects can be managed with dose modification and supportive care, according to the abstract.
“We’re still accruing on the phase 2 portion of the study, so we don’t have a long follow-up, but used in the carfilzomib in [combination] with selinexor was relatively safe, had manageable toxicity and was extremely effective, including in patients with a little bit more resistant disease,” Gasparetto told Healio.
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Gasparetto C, et al. Abstract 8530. Presented at: ASCO20 Virtual Scientific Program; May 28-31, 2020.
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