Oral Selinexor–Dexamethasone for Triple-Class Refractory Multiple Myeloma

• Published in: The New England journal of medicine Vol. 381; no. 8; pp. 727 - 738
• Main Authors: Chari, Ajai, Vogl, Dan T, Gavriatopoulou, Maria, Nooka, Ajay K, Yee, Andrew J, Huff, Carol A, Moreau, Philippe, Dingli, David, Cole, Craig, Lonial, Sagar, Dimopoulos, Meletios, Stewart, A. Keith, Richter, Joshua, Vij, Ravi, Tuchman, Sascha, Raab, Marc S, Weisel, Katja C, Delforge, Michel, Cornell, Robert F, Kaminetzky, David, Hoffman, James E, Costa, Luciano J, Parker, Terri L, Levy, Moshe, Schreder, Martin, Meuleman, Nathalie, Frenzel, Laurent, Mohty, Mohamad, Choquet, Sylvain, Schiller, Gary, Comenzo, Raymond L, Engelhardt, Monika, Illmer, Thomas, Vlummens, Philip, Doyen, Chantal, Facon, Thierry, Karlin, Lionel, Perrot, Aurore, Podar, Klaus, Kauffman, Michael G, Shacham, Sharon, Li, Lingling, Tang, Shijie, Picklesimer, Carla, Saint-Martin, Jean-Richard, Crochiere, Marsha, Chang, Hua, Parekh, Samir, Landesman, Yosef, Shah, Jatin, Richardson, Paul G, Jagannath, Sundar
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 22.08.2019
• Subjects: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; Appetite loss; Biomarkers; Biomarkers, Tumor - blood; Bortezomib; Cancer therapies; Cytogenetics; Dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Drug Administration Schedule; Drug dosages; Drug Resistance, Neoplasm; Exportin 1 Protein; FDA approval; Female; Humans; Hydrazines - administration & dosage; Hydrazines - adverse effects; Immunomodulation; Immunotherapy; Inhibitor drugs; Intention to Treat Analysis; Karyopherins - antagonists & inhibitors; Male; Middle Aged; Monoclonal antibodies; mRNA; Multiple myeloma; Multiple Myeloma - drug therapy; Nausea; Nuclear transport; Patients; Pharmaceuticals; Proteasome inhibitors; Proteins; Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors; Steroids; Survival; Survival Analysis; Targeted cancer therapy; Thrombocytopenia; Thrombocytopenia - chemically induced; Triazoles - administration & dosage; Triazoles - adverse effects; Tumor suppressor genes; Young Adult
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1903455

Selinexor, a drug that inhibits nuclear export of tumor suppressor proteins, was tested in a phase 2 trial involving patients with myeloma whose disease had progressed despite treatment with proteasome inhibitors, immunomodulatory agents, alkylating agents, and monoclonal antibodies. A partial response or better was observed in 26% of patients, and the median overall survival was 8.6 months.