Issue: June 25, 2018
May 01, 2018
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Selinexor shows promise for penta-refractory multiple myeloma

Issue: June 25, 2018
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Selinexor conferred a promising overall response rate among patients with multiple myeloma in a single-arm phase 2b study, according to the agent’s manufacturer.

The international STORM study included 122 heavily pretreated patients with penta-refractory myeloma.

Researchers characterized penta-refractory patients as:

  • those who previously received at least one alkylating agent, glucocorticoids, the two immunomodulatory drugs lenalidomide (Revlimid, Celgene) and pomalidomide (Pomalyst, Celgene), the two proteasome inhibitors bortezomib (Velcade, Takeda Oncology/Millennium) and carfilzomib (Kyprolis, Amgen), and the anti-CD38 monoclonal antibody daratumumab (Darzalex, Janssen);
  • those whose disease was refractory to glucocorticoids, at least one proteasome inhibitor, at least one immunomodulatory drug and daratumumab; and
  • those whose disease has progressed following their most recent therapy.

“Despite numerous advances in myeloma treatment, currently available therapies are insufficient to address the increasing number of patients with highly resistant, penta-refractory myeloma, [in which] the disease has ultimately become nonresponsive to approved therapy,” Paul G. Richardson, MD, director of clinical research of the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute and a HemOnc Today Editorial Board Member, said in a company-issued press release. “There is, therefore, a real urgency for new therapies with novel mechanisms of action for these patients, who have a critical unmet medical need.”

In the STORM trial, patients received 80 mg oral selinexor (KPT-330, Karyopharm Therapeutics) twice weekly in combination with low-dose 20 mg dexamethasone.

Results showed an ORR of 25.4%, which included two patients who achieved complete responses and 29 patients who achieved partial or very good partial responses. Median duration of response was 4.4 months.

Selinexor’s safety profile appeared consistent with previous studies of the agent. The most common adverse events included nausea, vomiting, fatigue and reduced appetite, most of which were low grade and manageable.

The most common hematologic adverse events were grade 3 or higher cytopenias, but these generally did not appear associated with clinical sequelae.

Efficacy and safety results will be submitted for presentation at a medical meeting.

“The 25.4% response rate and 4.4-month duration of response observed in the STORM study are highly compelling,” Sundar Jagannath, MD, director of the multiple myeloma program and professor of medicine at Tisch Cancer Institute at Mount Sinai School of Medicine, said in the release. “For an orally administered therapy, these new data underscore selinexor’s potential to be an exciting new treatment option for these difficult-to-treat patients who have exhausted approved therapies.”

The FDA granted orphan drug designation to selinexor for multiple myeloma and fast track designation to the agent in the penta-refractory setting.