Combination Drug Shows Efficacy in Tough-to-Treat Blood Cancer

Multiple Myeloma

Researchers may have found a solution to treating a bone marrow cancer that has proven to be resistant to several standard therapies.

Using a recently approved drug, researchers from Mount Sinai conducted a study of selinexor with dexamethasone in patients with multiple myeloma who have not responded to previous treatments and the results were quite promising. The combination of the two drugs “significantly knocked down the cancer in more than a quarter of patients, including two patients who went into complete remission,” the researchers said. Last month, the combination of selinexor and dexamethasone was approved by the U.S. Food and Drug Administration for the treatment of patients with relapsed or refractory multiple myeloma who have undergone previous rounds of treatment. The combination therapy, approved under the brand name Xpovio, was awarded to Karyopharm Therapeutics.

The results of the Mount Sinai study were published in The New England Journal of Medicine. The Mount Sinai researchers said selinexor has an unprecedented mechanism that blocks the export of protein and messenger RNAs from the nucleus of the cancer cell to the cytoplasm, which causes the cancer cell to die. The combination treatment caused at least a minimal response in almost 40 percent of patients who had multiple myeloma, a cancer of a type of white blood cell called a plasma cell, the researchers said in their announcement.

Sundar Jagannath, director of the multiple myeloma program and professor of medicine at the Tisch Cancer Institute at Mount Sinai, said the study showed a novel, first-in-class drug with a new mechanism of action can kill a patient's cancer cells. Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. The Mount Sinai trial provide the drug worked in patients who had exhausted other treatment options and would have likely died in hospice, Jagannath said.

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The clinical trial, called the STORM Part 2 Study, studied the response of 122 patients taking selinexor and dexamethasone, both oral drugs, in trials across the United States and Europe. The data shows that patients typically responded to the combination within one or two months. While there was no organ toxicity, side effects included low blood count without bleeding, nausea, vomiting, lack of appetite or fatigue. While Mount Sinai conducted the study, Karyopharm provided some of the funding. Selinexor is also being investigated in multiple myeloma in combination with other approved multiple myeloma drugs as well as in other malignancies such as lymphoma and ovarian cancer.

Xpovio’s approval was based on data from the Phase IIb STORM trial that included 123 patients with RRMM who had received at least three prior treatments. Trial data showed an overall response rate of 25.3 percent, which included 23 patients who experience a partial response. Sundar Jagannath, director of the multiple myeloma program at Tisch Cancer Institute at Mount Sinai School of Medicine and principal investigator of the STORM trial, said the 25.3% response rate “is clinically meaningful and a validated surrogate marker for clinical benefit in our patients with advanced refractory disease.”

Ajai Chari, director of clinical research in the multiple myeloma program at Tisch, said the STORM Part 2 study is meaningful for those patients who have not had success with other therapies. For patients who have not responded to previous drugs, the overall survival time is quite short, sometimes less than three months, Chari said.

The Tisch Cancer Institute recently launched a new Center of Excellence for Multiple Myeloma, which brings together experts from around the world to advance innovative research and personalized treatments for the disease. Jagannath serves as director of the center.

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