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Doc reports ‘very encouraging’ results in penta-refractory MM


 

Photo by Bill Branson

Vials of drugs

HOUSTON—Treatment with selinexor and low-dose dexamethasone can provide a “meaningful clinical benefit” in patients with penta-refractory multiple myeloma (MM), according to the principal investigator of the STORM trial.

Updated results from this phase 2 trial showed that selinexor and low-dose dexamethasone produced an overall response rate of 26.2% and a clinical benefit rate of 39.3%.

The median progression-free survival was 3.7 months, and the median overall survival was 8.6 months.

The trial’s principal investigator, Sundar Jagannath, MBBS, of the Mount Sinai School of Medicine in New York, N.Y., presented these results at the Society of Hematologic Oncology (SOHO) 2018 Annual Meeting as abstract MM-255.*

“The additional phase 2b clinical results ... are very encouraging for the patients suffering from penta-refractory multiple myeloma and their families,” Dr. Jagannath said.

“Of particular significance, for the nearly 40% of patients who had a minimal response or better, the median survival was 15.6 months, which provided the opportunity for a meaningful clinical benefit for patients on the STORM study.”

The study (NCT02336815) included 122 patients with penta-refractory MM. They had previously received bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, alkylating agents, and glucocorticoids. Their disease was refractory to glucocorticoids, at least one proteasome inhibitor, at least one immunomodulatory drug, daratumumab, and their most recent therapy.

The patients had received a median of 7 (range, 3-18) prior treatment regimens. Their median age was 65 (range, 40-86), 58% were male, and 53% had high-risk cytogenetics.

Patients received oral selinexor at 80 mg twice weekly plus dexamethasone at 20 mg twice weekly until disease progression.

Response and survival

Two patients (1.6%) achieved stringent complete responses. They also had minimal residual disease negativity, one at the level of 1 x 10-6 and one at 1 x 10-4.

Six patients (4.9%) had very good partial responses, 24 (19.7%) had partial responses (PRs), 16 (13.1%) had minimal responses (MRs), and 48 (39.3%) had stable disease (SD).

Sixteen patients (13.1%) had progressive disease (PD), and 10 (8.2%) were not evaluable for response.

The overall response rate (PR or better) was 26.2% (n=32), the clinical benefit rate (MR or better) was 39.3% (n=48), and the disease control rate (SD or better) was 78.7% (n=98).

The median duration of response was 4.4 months (range, <1 to 12.2 months).

The median progression-free survival was 3.7 months overall, 4.6 months in patients with an MR or better, and 1.1 months in patients who had PD or were not evaluable.

The median overall survival was 8.6 months for the entire cohort. It was 15.6 months in patients with an MR or better and 1.7 months in patients who had PD or were not evaluable (P<0.0001).

Safety

The most common non-hematologic treatment-related adverse events (AEs) were fatigue/asthenia (69.9%), nausea (69.1%), anorexia (52.0%), weight loss (47.2%), vomiting (35.0%), diarrhea (33.3%), and hyponatremia (30.9%).

Hematologic treatment-related AEs included thrombocytopenia (67.5%), anemia (48.0%), neutropenia (35.8%), leukopenia (29.3%), and lymphopenia (13.8%).

The “most important” grade 3/4 AEs, according to Dr. Jagannath, were thrombocytopenia (53.7%), anemia (29.3%), fatigue (22.8%), hyponatremia (16.3%), nausea (9.8%), diarrhea (6.5%), anorexia (3.3%), and emesis (3.3%).

Twenty-three patients (19.5%) discontinued treatment due to a related AE.

This study was sponsored by Karyopharm Therapeutics. Dr. Jagannath reported relationships with Karyopharm, Janssen, Celgene, Amgen, and GSK.

*Information in the abstract differs from the presentation.

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