SELINEXOR OPENS OPTIONS TO TREAT REFRACTORY MYELOMA.

 
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A novel agent called Selinexor has opened up new options for the treatment of patients with refractory myeloma. This was the conclusion of a major international clinical trial in which also the Karl Landsteiner University of Health Sciences in Krems, Austria (KL Krems) participated. The results have now been published in the New England Journal of Medicine. Thanks to a new mode of action, the compound brings hope to the growing number of patients whose tumor cells have become resistant to the three backbone drug classes.

Multiple myeloma is the second most common form of hematologic malignancies. Besides autologous stem cell transplantation for fit patients and conventional chemotherapy drugs, three classes of agents, which are optimally combined, form the backbone of myeloma therapy: immunomodulatory drugs (IMiDs), proteasome inhibitors, and monoclonal antibodies. If patients develop resistance against one of these types of medication, they often switch to another. At present, no further drug treatment is available for the increasing number of myeloma patients resistant against all three drug classes thereby precluding further improvement of patient survival. However, an international team including KL Krems' Dr. Klaus Podar (from the Department of Internal Medicine 2, Krems University Hospital) has now uncovered a medication that opens the door to a new treatment option.

More than a quarter of myeloma patients in our trial responded positively to the treatment with the new agent, Selinexor, in combination with dexamethasone, an immunosuppressant, said Klaus Podar, commenting on the study's key finding. The primary endpoint was overall response defined as a confirmed partial response (= 50% reduction in serum protein of myeloma protein). Due to these exciting results, Selinexor was recently authorized in the USA following an accelerated approval procedure. A total of 122 patients from Europe and the USA took part in the phase 2b clinical trial. On average, they were 65 years old and had suffered from myeloma for over six years. All patients had undergone between three and 18 treatment regimens and progressed. All of the subjects received the new drug in combination with dexamethasone.

Selinexor is an attractive alternative primarily because its mode of action is completely new. It is based on inhibition of exportin-1 (XPO-1), a protein responsible for transporting molecules associated with tumor cell proliferation from the cell's nucleus...

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