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Selinexor FDA Submission Started for Multiple Myeloma

Jason M. Broderick @jasoncology
Published: Wednesday, Jul 18, 2018

A rolling submission of an FDA new drug application (NDA) has been submitted for selinexor for the treatment of patients with penta-refractory multiple myeloma, according to Karyopharm Therapeutics, the manufacturer of the XPO1 inhibitor.

In the quad-refractory group, the median age was 62 years (range, 41-78), the median number of prior regimens was 7 (range, 3-16), and the median duration from diagnosis was 4 years (range, 1-6). Eighty-three percent of patients received the 6-dose regimen and 17% of patients received the 8-dose regimen.

Among the penta-refractory cohort, the median age was 68 years (range, 34-78), the median number of prior regimens was 7 (range, 5-17), and the median duration from diagnosis was 4 years (range, <1-35). Thirty-five percent of patients received the 6-dose regimen and 65% of patients received the 8-dose regimen.

The clinical benefit rate (CBR; defined as VGPR + PR + minor response [MR]) was 33% in the overall population. The VGPR, PR, and MR rates were 5%, 15%, and 13%, respectively. The stable disease (SD) and progressive disease (PD) rates were 35% and 12%, respectively.

In quad-refractory patients the CBR was 29%, comprising VGPR, PR, and MR, rates of 4%, 17%, and 8%, respectively. The SD and PD rates were 44% and 8%, respectively. In penta-refractory patients, the CBR was 40%, comprising VGPR, PR, and MR rates of 7%, 13%, and 20%, respectively. The SD and PD rates were 20% and 17%, respectively.

Among patients receiving the 6-dose regimen, the ORR was 20%. The CBR was 29%, comprising VGPR, PR, and MR rates of 6%, 14%, and 10%, respectively. The SD and PD rates were 41% and 8%, respectively. In those receiving the 8-dose regimen, the ORR was 22%. The CBR was 41%, comprising VGPR, PR, and MR rates of 4%, 19%, and 19%, respectively. The SD and PD rates were 22% and 19%, respectively. 

In patients with del(17p), the ORR 38%. The CBR was 63%, comprising VGPR, PR, and MR rates of 13%, 25%, and 25%, respectively. The SD and PD rates were 25% and 13%, respectively.

The median time to response was 1 month and the median duration of response was 5 months. Among patients who achieved at least an MR, the median OS was not reached and the median PFS was 5.5 months.

The most common all-grade adverse events (AEs) included nausea (73%), thrombocytopenia (73%), fatigue (63%), anorexia (49%), anemia (49%), vomiting (44%), diarrhea (43%), hyponatremia (42%), weight loss (33%), leukopenia (32%), neutropenia (24%), lymphopenia (14%), dehydration (11%), and dysgeusia (11%).

Grade 3 AEs occurring at the highest rates included anemia (27%), thrombocytopenia (25%), hyponatremia (22%), fatigue (15%), and leukopenia (13%). Grade 4 AEs included thrombocytopenia (34%), neutropenia (6%), anemia (1%), leukopenia (1%), and lymphopenia (1%).

Selinexor dose modifications included interruptions, reductions, and discontinuations in 52%, 37%, and 18% of patients, respectively.

Selinexor inhibits XPO1, levels of which cancer cells increase in order to transfer tumor-suppressor proteins out of the nucleus, leading to inactivation of these cancer-fighting proteins. High levels of XPO1 also promote production of oncoproteins that fuel the growth of the tumor. Selinexor’s mechanism of blocking XPO1, limiting the production of oncoproteins, and preventing the transfer of tumor-suppressor proteins out of the nucleus has emerged as a promising strategy.

The ongoing phase III BOSTON trial (NCT03110562) is randomizing patients to a triplet combination of selinexor, bortezomib, and the dexamethasone versus a combination of bortezomib and dexamethasone in patients with relapse/refractory multiple myeloma who have received 1 to 3 prior anti–multiple myeloma regimens.
Vogl DT, Dingli D, Cornell RF, et al. Selinexor and low dose dexamethasone (Sd) in patients with lenalidomide, pomalidomide, bortezomib, carfilzomib and anti-CD38 Ab refractory multiple myeloma (MM): STORM study. Presented at: 58th American Society of Hematology Annual Meeting; San Diego, CA; December 3-6, 2016. Abstract 491.

 



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Community Practice Connections™: 22nd Annual International Congress on Hematologic Malignancies®: Focus on Leukemias, Lymphomas and MyelomaMay 30, 20192.0
Medical Crossfire®: Personalizing Care for Multiple Myeloma Patients: Current and Future Sequencing StrategiesMay 31, 20191.5
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