Cancer – New Inhibitor Effective Where Others Fail
CANCER: NEW INHIBITOR EFFECTIVE WHERE OTHER TREATMENTS FAIL Investigation of targeted treatment in refractory myeloma patients: scientists from Karl Landsteiner University of Health Sciences part of team behind international study.
Krems (Austria), 3. December 2019 – 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 (its “power plant”) to its cytoplasm. In addition, Selinexor activates tumor suppressor proteins in the cell nucleus. As a result Selinexor kills cancer cells. The drug, which is available in tablet form, will bring new hope, especially to patients who have undergone various treatments in the past, and for whom there are practically no other options available; as Klaus Podar points out: “The medication has the potential to be a new treatment option for those patients who have failed other therapies.”
In Podar’s view, accelerated approval of the drug in the US shows just how effective targeted therapies can be under certain circumstances, as well as highlighting the importance of related research for the benefit of patients. Selinexor is only one of many new therapeutic approaches against myeloma that KL Krems oncology researchers are investigating. Others include combined therapies as part of autologous stem cell transplantation and targeted regulation of transcription factors. The ninth Oncology Day held recently at KL Krems gave experts an excellent overview of related activities currently under way, as well as underlining the university’s growing reputation as Lower Austria’s leading oncology center.
Original publication: Oral Selinexor–Dexamethasone for Triple-Class Refractory Multiple Myeloma. Ajai Chari, M.D. et al. N Engl J Med 2019; 381:727-738. DOI: 10.1056/NEJMoa1903455
About Karl Landsteiner University of Health Sciences Karl Landsteiner University of Health Sciences (KL) is a pioneer for innovation in medical and health sciences education and research, and a catalyst for groundbreaking work which will benefit society at large. Research at KL focuses on niche fields in bridge disciplines such as molecular oncology and hematology, biomedical engineering, psychology and psychodynamics, as well as topics including water quality and related health issues. Study programmes include health sciences, human medicine, psychology, psychotherapy and counselling and have full European recognition. A network of university hospitals in St PoeltenPölten, Krems, and Tulln provides students with quality-assured, research-led education; it. It enables them to do internationally- recognized top-class clinical and translational research that is recognised worldwide. Karl Landsteiner University received accreditation by the Agency for Quality Assurance and Accreditation Austria (AQ Austria) in 2013.
Priv.-Doz. Mag. DDr. Klaus Podar
Department of Internal Medicine 2
University Hospital Krems
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