Therapeutic 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 .

Alexandra Hospital School of Medicine National and Kapodistrian University of Athens Athens Greece

Baylor University Medical Center Dallas TX USA

Charbonneau Cancer Research Institute University of Calgary Calgary AB USA

Charles University and General Hospital Prague Czech Republic

Cherkassy Regional Oncological Center Cherkassy Ukraine

CHU Lille Service Des Maladies du Sang 59000 Lille France

City Clinical Hospital 40 Moscow Russian Federation

City Clinical Hospital No 4 of Dnipro City Council Dnipro Ukraine

Cross Cancer Institute University of Alberta Edmonton AB Canada

Dana Farber Cancer Institute Boston MA USA

Department of Hematology CHU La Miletrie and Inserm CIC 1402 Poitiers France

Department of Hematooncology University Hospital Ostrava Ostrava Czech Republic

General Hospital Evangelismos Athens Greece

Greenebaum Comprehensive Cancer Center University of Maryland Baltimore MD USA

Hospital Universitario de Salamanca Salamanca Spain

Hotel Dieu University Hospital Nantes France

Imperial College London London UK

Institute of Blood Pathology and Transfusion Medicine of NAMS of Ukraine Lviv Ukraine

Karyopharm Therapeutics Inc Newton MA USA

Kings College Hospital NHS Foundation Trust London UK

Medical University of Silesia Katowice Poland

National and Kapodistrian University of Athens Athens Greece

National Cancer Institute Kiev Ukraine

Nil Ratan Sircar Medical College and Hospital Kolkata India

Norton Cancer Institute St Matthews Campus Louisville KY USA

Seràgnoli Institute of Hematology Bologna University School of Medicine Bologna Italy

Simmons Comprehensive Cancer Center UT Southwestern Medical Center Dallas TX USA

St Vincent's Hospital University of Melbourne Melbourne VIC Australia

State Cancer Institute Indira Gandhi Institute of Medical Sciences Patna India

Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York NY USA

University Hospital Brno Brno Czech Republic

University Hospitals of Leicester NHS Trust Leicester UK

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ClinicalTrials.gov
NCT03110562