Selinexor is a first-in-class Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates Exportin 1 (XPO1). Selinexor with low dose dexamethasone (Xd) or in with protesome inhibitors (PIs) or immunomodulatory drugs (IMiDs), has shown anti-MM activity in patients (pts) with relapsed or refractory MM. Daratumumab (Dara), an anti-CD38 mAb, is approved for the treatment of heavily pretreated MM is limited by short PFS and an ORR of ~21% in quad-refractory MM. Selinexor in combination with dara have shown preclinical synergistic killing of MM cells. 

Selinexor 100 mg QW can be combined safely with dara (per approved dosing) and dex. The preliminary ORR of 74% with XDd in patients with PI/IMiD refractory MM who are dara naïve is promising and compares favorably to 21% ORR of Dara and Xd in quad refractory myeloma. This once weekly regimen is well tolerated with no major organ toxicities to date. Data from the full phase 1 dose expansion will be presented.

Authors:

Cristina J Gasparetto, MD, Suzanne Lentzsch, MD, Gary J. Schiller, MD, William Bensinger, MD, Nizar Bahlis, MD, Heather J. Sutherland, MD, PhD, Darrell J. White, MD, Michael Sebag, MD, PhD, Rami Kotb, MD, Christopher P. Venner, MD, FRCPC, Richard Leblanc, MD, FRCPC, Christine I Chen, MD, Aldo Del Col, Jatin J. Shah, MD, Jacqueline Jeha, Jean-Richard Saint-Martin, Michael G. Kauffman, MD, PhD, Sharon Shacham, PhD, MBA, Joel G. Turner, PhD, Daniel M Sullivan, MD and Brea Lipe, MD

ASH 2018 Abstract 599 "Deep and Durable Responses with Selinexor, Daratumumab, and Dexamethasome (XDd) in Patients with Multiple Myeloma (MM) Previously Exposed to Proteasome Inhibitors and Immunomodulatory Drugs: Results of Phase 1b Study of SDd"

ABOUT CRISTINA J. GASPARETTO, MD

Dr. Gasparetto performs both laboratory and clinical research in the field of multiple myeloma. Her research interests include developing immunotherapy approaches to treating multiple myeloma particularly in conjunction with hematopoietic stem cell transplantation. Dr. Gasparetto is also an investigator on several other clinical trials for myeloma including non-myeloablative allogeneic transplantation, high dose sequential chemotherapy and autologous peripheral blood stem cell transplantation and transplantation of partially HLA matched unrelated cord blood Visit Dr. Cristina Gasparetto’s full biography (https://medicine.duke.edu/faculty/cristina-gasparetto-md).