San Diego, CA—Selinexor has shown promising activity in very heavily pretreated patients with penta-refractory multiple myeloma. In the pivotal STORM Part 2 study, oral selinexor in combination with low-dose dexamethasone induced responses in 26.2% of patients.
The median progression-free survival was 3.7 months and the median overall survival was 8.6 months in patients who were exposed to at least 1 proteasome inhibitor, at least 1 immunomodulatory drug (ie, daratumumab [Darzalex]), and a glucocorticoid.
Selinexor is an oral selective inhibitor of exportin 1, which is the major nuclear export protein for tumor suppressor proteins and eIF4E-bound oncoprotein RNAs. Ajai Chari, MD, Director of Clinical Research, Multiple Myeloma Program, Mount Sinai School of Medicine, New York City, presented the study results at ASH 2018.
“STORM Part 2 represents the largest, most heavily pretreated population with multiple myeloma in a prospective clinical trial to date,” said Dr Chari. “Patients received a median of 7 prior therapies over 6.6 years. These patients have no known available therapies with clinical benefit.”
In time, all patients with refractory multiple myeloma are exposed to all 3 classes of current agents used in treatment of this disease, and the prognosis for triple-class disease is dismal, Dr Chari said.
“There are no approved drugs with established clinical activity in triple-class refractory myeloma,” he emphasized.
Triple-Class Refractory Disease
The STORM Part 2 study assessed continuous selinexor dosing in patients with penta-refractory and triple-drug-class–refractory multiple myeloma. The study enrolled 123 patients with multiple myeloma who previously received bortezomib (Velcade), carfilzomib (Kyprolis), pomalidomide (Pomalyst), daratumumab, an alkylator, and glucocorticoids. The study treatment consisted of selinexor 80 mg plus dexamethasone 20 mg twice weekly (on days 1 and 3) of a 28-day cycle.
The eligibility criteria included creatinine clearance levels ≥20 mL/min, neutrophil counts of ≥1000/mm3, platelet counts of ≥75,000/mm3 (or >50,000/mm3 if bone marrow plasma cells were >50%), and hemoglobin levels of ≥8.5 g/dL.
The median patient age was 65 years, and the median time from diagnosis was 6.6 years.
Approximately 30% of patients received ≥9 previous lines of therapy. “These are high-risk patients that are really sequencing through many lines of therapy in a short time,” Dr Chari said. Almost all (96%) of the patients had disease that was refractory to carfilzomib, pomalidomide, and daratumumab; 68% had penta-refractory multiple myeloma; and 84% had a previous stem-cell transplant.
At the data cutoff point, 5 (4.1%) patients remained on treatment and 118 (95.9%) had discontinued treatment, with 55.1% of the discontinuations a result of disease progression and 32.2% because of an adverse event. The investigators determined that 19.5% of the events were related to treatment with selinexor plus dexamethasone.
Of the 26.2% of patients who responded to treatment, 19.7% had a very good partial response and 6.5% had a very good partial response or better. The median time to response was 1 month, and the median duration of response was 4.4 months. Two patients had a stringent complete response, with minimum residual disease negativity at a level of 10–6 in 1 patient and 10–4 in the other.
The response rates were similar, regardless of the most recent previous therapy. In all, 71% of the patients who underwent evaluation had a reduction in myeloma protein levels.
Some 79.7% of patients required a dose modification, most often in the first 2 cycles. “Side effects were reversible, without evidence of major organ toxicities nor cumulative toxicity,” Dr Chari said.
The most frequent treatment-related nonhematologic adverse events were nausea (69.1%); anorexia (52%); vomiting (35%); diarrhea (33.3%); constitutional adverse events, such as fatigue (56.1%) and weight loss (47.2%); and hyponatremia (30.9%).
The most frequent grade 3 events were fatigue (18.7%), hyponatremia (16.3%), and nausea (9.8%); hematologic events included thrombocytopenia (67.5%), anemia (48%), neutropenia (36.6%), leukopenia (29.3%), and lymphopenia (13.8%).