Selinexor combination shows benefit in progression free survival

An all-oral regimen for patients with relapsed multiple myeloma appears to improve progression-free survival and overall response rate when compared with historical outcomes, researchers reported at the 2020 virtual meeting of the American Society of Hematology.

In his presentation, Darrell White, MD, professor of medicine at Dalhousie Medical University and QEII Health Sciences Centre, Halifax, Nova Scotia, reported that patients treated with selinexor (Xpovio), pomalidomide (Pomalyst) and dexamethasone achieved a progression free survival of 12.3 months.

One of the primary goals of the STOMP Phase 1b/Phase 2 study was to determine the recommended Phase 2 dose of the triplet therapy. White said that after considering 5 different regimens and dosing schedules, the researchers selected a regimen of once weekly selinexor 60 mg, plus once daily pomalidomide 4 mg taken on days 1 through 21 of a 28-day cycle, and once weekly dexamethasone 40 mg.

The secondary endpoint of progression free survival was 12.2 months among all of the 60 evaluable patients, White said in his presentation. The progression-free survival among the 46 patients who were naive to pomalidomide was 12.3 months; and the progression-free survival among the 14 patients who had previously been treated with pomalidomide was 8.8 months.

Importantly, the progression free survival among the 20 patients who were assigned to the regimen that will be taken into further testing has not yet been reached, he said.

White added that for all the patients in the trial, the duration of response was a median of 11.3 months, but the median duration of response for those patients taking what is believe to be the optimal dose has not yet been reached.

The overall response rate for all the patients in the study was 54.3%, White said. The response rate for those previously on pomalidomide was 35.7%; the overall response rate for the patients who were getting the recommended Phase 2 dose was 60%.

“The all oral selinexor/pomalidomide/dexamethasone combination appears to confer relatively high overall response rate with good durability and promising progression-free survival in patients with with heavily pretreated multiple myeloma,” the researchers reported.

Enrollment in the STOMP (Selinexor and Background Treatments of Multiple Myeloma Patients) trial was limited to patients diagnosed with multiple myeloma that was progressing despite treatment on at least two previous therapies, or who were refractory of other treatments. Entry criteria for the open-label trial required a minimum of previous treatment with lenalidomide and a proteasome inhibitor. Pomalidomide exposure was allowed in the expansion phase of the trial.

In commenting on the trial, Wasif Saif, MD, deputy physician-in-chief and medical director, at Northwell Health Cancer Institute, Lake Success, New York, told BreakingMED, “The results of this study showed an overall response rate of 58% in patients in lenalidomide refractory and pomalidomide naïve multiple myeloma compared to previously published data of 31% overall response rate for pomalidomide/dexamethasone in a similar patient population.

“Other parameters of efficacy are also very encouraging, including the median progression free survival on the triplet of 12.3 months in pomalidomide naïve patients in contrast to the historically observed median progression free survival of approximately 4 months with pomalidomide/dexamethasone,” Saif said.

He noted that the adverse side effect profile of the combination was expected and manageable with appropriate supportive care and/or dose modifications.

Saif said that being able to deliver the therapy orally may be a plus. “Oral administration enables convenient, patient-oriented, home-based therapy, which most patients prefer to intravenous treatment administered in the clinic,” he said. “In addition, oral therapy avoids the problems and inconvenience associated with venous access. Moreover, cost related to travel and other factors is omitted with oral medications.

“However, compliance issues have to be considered,” he said. “Additionally, if a patient is receiving an oral agent along with an intravenous drug, then they still need to have a intravenous catheter placed and come in for the intravenous drug.

“The new all oral selinexor/pomalidomide/dexamethasone regimen achieved an impressive response rate and progression free survival in this study,” Saif said. “This observed activity and manageable side effect profile supports further studies and could offer a new treatment option for patients with multiple myeloma.”

Selinexor is the first-in-class oral selective inhibitor of nuclear export which blocks XPO1, forcing the nuclear retention and activation of tumor suppressor proteins, ultimately causing apoptosis in cancer cells, the researchers explained.

The current FDA-approved indications for selinexor with dexamethasone includes treatment of adults with multiple myeloma that has relapsed or that did not respond to previous treatment, and who have received at least 4 prior therapies, and whose disease did not respond to at least 2 proteasome inhibitor medicines, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody medicine.

Selinexor is also approved to treat dif‌fuse large B-cell lymphoma.

The researchers have enrolled 65 patients into the STOMP trial, 33 men and 32 women. Their median age is 64 years; from diagnosis with multiple myeloma to treatment in the STOMP trial was about 4.4 years.

Common hematologic treatment related adverse events were neutropenia (60%); anemia (54%), and thrombocytopenia (54%). Common non-hematologic events included nausea, fatigue, decreased appetite, weight loss, diarrhea, and vomiting.

  1. Be aware that this activity discusses the off-label use of a drug.

  2. Note that the oral combination regimen in studied in this trial did improve progression-free survival in patients with relapsed multiple myeloma, but these preliminary results were presented at a medical meeting and should be interpreted with caution until published in a peer-reviewed journal.

Edward Susman, Contributing Writer, BreakingMED™

The study was sponsored by Karyopharm, Brookline, Massachusetts.

White disclosed relationships with Sanofi, Amgen, Karyopharm, Antegene, GlaxoSmithKline, Takeda, Janssen and Celgene.

Saif disclosed no relevant relationships with industry.

Cat ID: 116

Topic ID: 78,116,728,791,116,332,468,192,925,331

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