Selinexor is a novel, oral Selective Inhibitor of Nuclear Export (SINE) compound that blocks exportin 1 (XPO1). Selinexor treatment results in nuclear accumulation and activation of tumor suppressor proteins, inhibition of NF-kB, and translational suppression of several oncoprotein mRNAs (e.g., c-myc, cyclin D).Multiple myeloma (MM) remains incurable, and most patients (pts) eventually progress through standard drug classes of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), anti-CD38 mAbs and others. The increased use of combinations in MM treatment, (PIs/IMiDs/mAbs), has led to a growing number of pts with penta-refractory MM (pts that have been treated with bortezomib (bort), carfilzomib (carfil), lenalidomide (len), pomalidomide (pom) and daratumumab (dara)). Active novel therapies with different mechanisms of actions are needed to address this unmet medical need. Part 1 of STORM enrolled pts with both quad- (bort, carfil, len, pom, treated MM) or penta-refractory MM and demonstrated an overall response rate (ORR) of 21% (Vogl et al, JCO 2018). Based on these findings, the Pivotal Part 2 of STORM was initiated, enrolling an additional cohort of 122 patients with penta-refractory MM.
Results of the pivotal STORM Part 2 in penta (PI, IMiD, dara)-refractory MM demonstrated that oral selinexor plus low-dose dexamethasone (Sd) was highly active with an ORR of 26.2%. Importantly, responses were rapid and deep with 2 patients achieving sCRs (both MRD negative) in these heavily pre-treated penta-refractory MM pts (median 7 prior regimens, 53% high risk). AEs are a function of dose/schedule/disease severity and can be managed with dose modifications and supportive care. No major organ toxicity was observed and AEs were typically transient and reversible. Sd is an all-oral, first in class mechanism with novel MOA and represents a potential therapeutic option to the growing number of pts with penta-refractory MM who have exhausted approved therapies.
Ajai Chari, MD, Dan T. Vogl, MD, Meletios A Dimopoulos, MD, Ajay K Nooka, MD, MPH, Carol Ann Huff, MD, Philippe Moreau, Craig E. Cole, MD, Joshua Richter, David Dingli, MD, PhD, Ravi Vij, Sascha A Tuchman, MD, Marc S Raab, MD, PhD, Katja Weisel, MD, Michel Delforge, MD PhD, David Kaminetzky, MD, Robert Frank Cornell, MD, A Keith Stewart, James Hoffman, Kelly N. Godby, MD, Terri L Parker, MD, Moshe Levy, MD, Martin Schreder, MD, Nathalie Meuleman, PhD, MD, Laurent Frenzel, MD, PhD, Mohamad Mohty, MD, PhD, Choquet Sylvain, MD, Andrew J. Yee, MD, Maria Gavriatopoulou, MD, Luciano J Costa, MD, PhD, Jatin J. Shah, MD, Carla Picklesimer, Jean-Richard Saint-Martin, Lingling Li, Michael G. Kauffman, MD, PhD, Sharon Shacham, PhD, MBA, Paul Richardson and Sundar Jagannath
ASH 2018 Abstract 598 "Results of the Pivotal STORM Study (Part 2) in Penta-Refractory Multiple Myeloma (MM): Deep and Durable Responses with Oral Selinexor Plus Low Dose Dexamethasone in Patients with Penta Exposed and Triple Class-Refractory MM "
ABOUT AJAI CHARI, MD
Dr. Ajai Chari is an Associate Professor of Medicine, Director of Clinical Research in the Multiple Myeloma Program, and the Associate Director of Clinical Research, Mt Sinai Cancer Clinical Trials Office in New York. His main areas of focus are plasma cell disorders including multiple myeloma, AL amyloidosis, POEMS syndrome, plasmacytoma, and monoclonal gammopathies of undetermined significance (MGUS). View Dr. Ajai Chari’s full biography here.