According to data from the STOMP trial involving thirty-four patients, a triple regimen has been proven to induce durable responses in pretreated patients with relapsed/refractory multiple myeloma. A recent article in OncLive supports the theory that combination regimens have brought new and improved results to myeloma therapy. With a special focus on multiple myeloma, researchers believe that treatment with different mechanisms of action will improve patients’ response.
The combination that was investigated in the Phase 1b/2 STOMP trial (NCT02343042) consists of a regimen of daratumumab (Darzalex), dexamethasone, and selinexor (Xpovio). The triplet (SDd) demonstrated a response rate overall of sixty-nine percent with a clinical benefit of eighty-two percent.
The regimen produced a progression-free survival rate of 12.5 months.
About Multiple Myeloma (MM)
MM, a cancer of the bone marrow, is characterized by abnormalities in plasma cells which are a type of white blood cell. These abnormal cells multiply in the bone marrow and can cause severe skeletal destruction. Learn more about multiple myeloma here.
Selinexor is an oral inhibitor of XP01, a protein-encoding gene. In 2019 in response to results of the STORM trial, the FDA approved selinexor ‘conditionally’ combined with low dose dexamethasone for patients who had been treated unsuccessfully with three other types of therapy.
The combination of selinexor and dexamethasone prevents the transporting of molecular material through XPO1 creating an accumulation of tumor suppressor proteins that block cancer-causing genes.
Eighty-nine percent of STORM trial participants had serious drug-related adverse events. This prompted a vote of 8 to 5 by the FDA panel against full approval. The new STOMP trial was based on the FDA’s approval of the Phase 2b STORM trial.
The Phase 1b/2 STOMP Trial
One end result of the multi-center trial is to determine the maximum dose of SDd that can be tolerated by participants and the recommended dose for phase 2 of the trial. Other endpoints are:
- Overall response rate
- Maximum tolerated dose
- Progression-free survival
- Duration of response
In order to enroll, patients must have been treated unsuccessfully with three or more drugs including an immunomodulatory drug (IMID) and a proteasome inhibitor (PI).
Thirty-four patients, median age of 68, were enrolled in the Phase 2 trial as of January 2020. Thirty-one patients received the recommended dose of 100 mg of selinexor and 16 mg of daratumumab once each week. Three patients were treated with selinexor (60 mg.) twice each week and 16 mg of daratumumab once each week.
Since there were no reported toxicities requiring dose reduction, the recommended dose for selinexor was 100 mg once each week. Selinexor would be combined with dexamethasone and daratumumab as planned.
About Triplet Safety
Over ten percent of patients receiving the recommended dose had adverse events related to the treatment. Most common were low platelets (thrombocytopenia 70.6%), low neutrophils (neutropenia 50%), and anemia (61.8%). Weight loss, fatigue, dizziness, and gastrointestinal adverse events were reported.
Nine patients experienced one or more severe adverse events that included rhinovirus infection, low platelets, pneumonia, and kidney injury. Other related events were various degrees of fatigue, diarrhea, low potassium, nausea, infusion-related reactions, and vomiting. Most blood-related disorders were manageable through dose reductions or interruptions.
In conclusion, it is evident that the selinexor triplet demonstrates promising clinical activity in treating relapsed/refractory multiple myeloma.