Dr. Gary Schiller, UCLA David Geffen School of Medicine, presents the results of once weekly Selinexor, Carfilzomib and Dexamethasone in triple class refractory multiple myeloma.
Background:
Selinexor, an oral exportin-1 inhibitor, is approved for the treatment of relapsed/refractory multiple myeloma (RRMM) in combination with either dexamethasone (Xd) or bortezomib and dexamethasone (XVd). Despite recent advances, multiple myeloma remains incurable and becomes resistant to current treatments, leaving a need for effective therapies. Selinexor works by blocking nuclear export and accumulating tumor suppressor proteins in the nucleus, leading to a reduction in oncogene protein translation. Results from clinical studies show that the combination of selinexor, bortezomib, and dexamethasone (XVd) has a median progression-free survival of 13.93 months, compared to 9.46 months with twice-weekly Vd. A combination of selinexor with another proteasome inhibitor, carfilzomib, has also shown impressive efficacy, including in triple-class refractory patients, with an overall response rate of 78%. Selinexor-containing regimens provide long-lasting disease control with good tolerability.
Conclusions:
The results of a small study highlight the potential of XKd as a treatment regimen for triple-class refractory multiple myeloma (TCR MM). XKd was well-tolerated in TCR MM patients with a manageable side-effect profile and a median duration of response of 12 months. These results are better compared to the MAMMOTH study where patients with TCR MM had an overall response rate of 31% and median progression-free survival of 3.4 months with standard treatments. The best results in the MAMMOTH study (47% ORR and 5.7 months mPFS) were seen in patients treated with carfilzomib-alkylator combinations.
Authors:
Gary J. Schiller, MD, Sascha A. Tuchman, MD, MHS, Natalie Callander, MD, Muhamed Baljevic, MD, Adrianna C Rossi, MD, Rami Kotb, MD, FRCPC, Darrell J White, MD, Nizar J. Bahlis, MD, Heather J. Sutherland, MD, PhD, FRCPC, Sumit Madan, MD, Richard Leblanc, MD, FRCPC, Christopher P. Venner, MD, William I. Bensinger, MD, Dane R. Van Domelen, PhD, Chris Zhang, MD, Ohad S. Bentur, MD MHA and Brea Lipe, MD
ASH Abstract #4516: https://ash.confex.com/ash/2022/webprogram/Paper158011.html
