Effect of prior treatments on selinexor, bortezomib, and dexamethasone in previously treated multiple myeloma

Springer Science and Business Media LLC - 2021
María Victoria Mateos1, Maria Gavriatopoulou2, Thierry Facon3, Holger W. Auner4, Xavier Leleu5, Roman Hájek6, Meletios A. Dimopoulos7, Sosana Delimpasi8, Maryana Simonova9, Ivan Špıčka10, Luděk Pour11, Iryna Kriachok12, Halyna Pylypenko13, Vadim Doronin14, Ganna Usenko15, Reuben Benjamin16, Tuphan Kanti Dolai17, Dinesh Kumar Sinha18, Christopher P. Venner19, Mamta Garg20, Don Stevens21, Hang Quach22, Sundar Jagannath23, Philippe Moreau24, Moshe Levy25, Ashraf Badros26, Larry D. Anderson27, Nizar J. Bahlis28, Michèle Cavo29, Yi Chai30, Jacqueline Jeha30, Melina Arazy30, Jatin J. Shah30, Sharon Shacham30, Michael Kauffman30, Paul G. Richardson31, Sebastian Grosicki32
1Hospital Universitario de Salamanca, Salamanca, Spain
2Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
3CHU Lille Service Des Maladies du Sang, 59000, Lille, France
4Imperial College London, London, UK
5Department of Hematology, CHU la Miletrie and Inserm CIC 1402, Poitiers, France
6Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic
7National and Kapodistrian University of Athens, Athens, Greece
8General Hospital Evangelismos, Athens, Greece
9Institute of Blood Pathology and Transfusion Medicine of NAMS of Ukraine, Lviv, Ukraine
10Charles University and General Hospital, Prague, Czech Republic
11University Hospital Brno, Brno, Czech Republic
12National Cancer Institute, Kiev, Ukraine
13Cherkassy Regional Oncological Center, Cherkassy, Ukraine
14City Clinical Hospital #40, Moscow, Russian Federation
15City Clinical Hospital No. 4 of Dnipro City Council, Dnipro, Ukraine
16Kings College Hospital NHS Foundation Trust, London, UK
17Nil Ratan Sircar Medical College and Hospital, Kolkata, India
18State Cancer Institute, Indira Gandhi Institute of Medical Sciences, Patna, India
19Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada
20University Hospitals of Leicester NHS Trust, Leicester, UK
21Norton Cancer Institute, St. Matthews Campus, Louisville, KY, USA
22St. Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia.
23Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
24Hotel-Dieu, University Hospital, Nantes, France
25Baylor University Medical Center, Dallas, TX, USA
26Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, USA
27Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA
28Charbonneau Cancer Research Institute, University of Calgary, Calgary, AB, USA
29"Seràgnoli" Institute of Hematology, Bologna University School of Medicine, Bologna, Italy
30Karyopharm Therapeutics Inc, Newton, MA, USA
31Dana Farber Cancer Institute, Boston, MA, USA
32Medical University of Silesia, Katowice, Poland

Tóm tắt

AbstractTherapeutic regimens for previously treated multiple myeloma (MM) may not provide prolonged disease control and are often complicated by significant adverse events, including peripheral neuropathy. In patients with previously treated MM in the Phase 3 BOSTON study, once weekly selinexor, once weekly bortezomib, and 40 mg dexamethasone (XVd) demonstrated a significantly longer median progression-free survival (PFS), higher response rates, deeper responses, a trend to improved survival, and reduced incidence and severity of bortezomib-induced peripheral neuropathy when compared with standard twice weekly bortezomib and 80 mg dexamethasone (Vd). The pre-specified analyses described here evaluated the influence of the number of prior lines of therapy, prior treatment with lenalidomide, prior proteasome inhibitor (PI) therapy, prior immunomodulatory drug therapy, and prior autologous stem cell transplant (ASCT) on the efficacy and safety of XVd compared with Vd. In this 1:1 randomized study, enrolled patients were assigned to receive once weekly oral selinexor (100 mg) with once weekly subcutaneous bortezomib (1.3 mg/m2) and 40 mg per week dexamethasone (XVd) versus standard twice weekly bortezomib and 80 mg per week dexamethasone (Vd). XVd significantly improved PFS, overall response rate, time-to-next-treatment, and showed reduced all grade and grade ≥ 2 peripheral neuropathy compared with Vd regardless of prior treatments, but the benefits of XVd over Vd were more pronounced in patients treated earlier in their disease course who had either received only one prior therapy, had never been treated with a PI, or had prior ASCT. Treatment with XVd improved outcomes as compared to Vd regardless of prior therapies as well as manageable and generally reversible adverse events. XVd was associated with clinical benefit and reduced peripheral neuropathy compared to standard Vd in previously treated MM. These results suggest that the once weekly XVd regimen may be optimally administered to patients earlier in their course of disease, as their first bortezomib-containing regimen, and in those relapsing after ASCT.Trial registration: ClinicalTrials.gov (NCT03110562). Registered 12 April 2017. https://clinicaltrials.gov/ct2/show/NCT03110562.

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