Today, the U.S. Food and Drug Administration granted accelerated approval to Xpovio (selinexor) tablets in combination with the steroid dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is resistant to several other forms of treatment, including at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.
This provide an all-oral option for highly relapsed and refractory patients whose myeloma has become resistant to the most commonly used myeloma therapies.
“While there is no cure for multiple myeloma, there are FDA-approved treatments to target the cancer and slow down the spread of the disease. Sadly, often over time, patients can exhaust all available treatments and still see their disease progress,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Today we approved a treatment under our accelerated approval program that provides a treatment option for patients with multiple myeloma with no available therapy.”
Approval was based on the STORM data of 83 patients with relapsed or refractory myeloma who were treated with selinexor with dexamethasone. The overall response rate was 25.3% and the median duration of response was 3.8 months. Overall survival was 8.6 months.
Common side effects of patients taking Xpovio in combination with dexamethasone include a low white blood cell count (leukopenia), a low count of neutrophils, a type of white blood cell (neutropenia), low count of platelets (thrombocytopenia) and low amount of red blood cells (anemia). Patients also reported vomiting, nausea, fatigue, diarrhea, fever, decreased appetite and weight, constipation, upper respiratory tract infections and low blood sodium levels (hyponatremia).
The side effects can be managed with supportive care such as anti-nausea medication and health care professional are advised to monitor patients for low blood counts, platelets and sodium levels. Patients should stay hydrated and avoid taking Xpovio with other medications that may cause dizziness or confusion and avoid situations where dizziness may be a problem. Contraception should be used during treatment with Xpovio and it should not be used for women who are pregnant or breastfeeding.
Xpovio was granted both Orphan Drug and Fast Track designation by the FDA because of the urgent unmet need in the clinic. According to Ajai Chari, MD of Mt. Sinai:
The treatment of triple class refractory multiple myeloma (ie those patients who are refractory to proteasome inhibitors, immunomodulatory agents, and anti-CD38 antibody therapy) is truly an unmet medical need. Until today, these patients have no FDA approved treatment options. The accelerated approval of selinexor, based on the STORM study of 123 enrolled patients achieving a response rate of 26.2% , is important, as its target, XPO1, is novel and this oral medication is a first-in-class agent. In addition to this approval in combination with dexamethasone, there are also encouraging preliminary data from ongoing triplet combination studies as well.
Myeloma patients who have relapsed after both IMiDs (lenalidomide and pomalidomide) and two proteasome inhibitors (bortezomib, ixazomib or carfilzomib) and a monoclonal antibody (like daratumumab) are considered “penta-refractory.” These patients must either go back to older chemotherapies like bendamustine or try to join immunotherapy clinical trials (like the CAR T therapies). Many if not most will not qualify for trials at this stage due to strict eligibility criteria and other health issues they typically have by that point.
According to myeloma expert Paul Richardson, MD of the Dana Farber Cancer Institute:
“For our patients in whom all major classes of drugs have failed, selinexor offers a unique mechanism of action as a next generation novel agent, and has demonstrated efficacy in the setting of heavily pre-treated advanced, relapsed and refractory multiple myeloma. I am also encouraged by the combination data, and very hopeful with careful attention to side effect management and supportive care, we will see meaningful clinical benefit from its use.”
More clinical trials are underway using selinexor in combination with other myeloma therapies. If you are taking selinexor, please talk with your doctor about how to best mitigate the side effects, as they are not permanent and can most often be managed with proper care. This is good news for patients who have few options for continued myeloma care.