BACKGROUND: The increasing use of anti-CD38 monoclonal antibodies (αCD38 mAbs) for newly diagnosed or early relapsed multiple myeloma (MM), especially in non-transplant eligible patients, may lead to more patients developing αCD38 mAb-refractory disease earlier in the treatment course with fewer treatment options. PATIENTS AND METHODS: We analyzed the efficacy and safety of selinexor-based triplets (selinexor+dexamethasone [Sd] plus pomalidomide [SPd, n = 23], bortezomib [SVd, n = 16] or carfilzomib (SKd, n = 23]) in a subset of STOMP (NCT02343042) and BOSTON (NCT03110562) study patients treated previously with αCD38 mAbs. RESULTS: Sixty-two patients (median 4 prior therapies, range 1 to 11, 90.3% refractory to αCD38 mAb) were included. Overall response rates (ORR) in the SPd, SVd and SKd cohorts were 52.2%, 56.3%, and 65.2%, respectively. Overall response rate was 47.4% among patients who had MM refractory to the third drug reintroduced in the Sd-based triplet. Median progression-free survival in the SPd, SVd, and SKd cohorts was 8.7, 6.7, and 15.0 months, respectively, and median overall survival was 9.6, 16.9, and 33.0 months, respectively. Median time to discontinuation in the SPd, SVd, and SKd cohorts was 4.4, 5.9, and 10.6 months, respectively. The most common hematological adverse events were thrombocytopenia, anemia, and neutropenia. Nausea, fatigue, and diarrhea were primarily grade 1/2. Adverse events were generally manageable with standard supportive care and dose modifications. CONCLUSION: Selinexor-based regimens may offer effective and well-tolerated therapy to patients with relapsed and/or refractory MM who had disease previously exposed or refractory to αCD38 mAb therapy and could help address the unmet clinical need in these high-risk patients.

1st Department of Medicine Department of Hematology 1st Faculty of Medicine Charles University and General Hospital Prague Czech Republic

CancerCare Manitoba Winnipeg MB Canada

Charbonneau Cancer Research Institute Calgary AB Canada; Clinical Research Unit Tom Baker Cancer Center Calgary AB Canada

David Geffen School of Medicine University of California Los Angeles Los Angeles CA

Department of Cellular Biotechnology and Hematology Hematology Center Umberto 1 Polyclinic of Rome Rome Italy

Department of Hematology and Cancer Prevention Medical University of Silesia Katowice Poland

Department of Hematology Hôpital Huriez CHU Lille France

Department of Hematology Vall d'Hebron University Hospital Barcelona Spain

Department of Internal Medicine 5 Medical University Innsbruck Innsbruck Austria

Duke University Cancer Center Durham NC

Hackensack Meridian Health Hackensack University Medical Center Hackensack NJ

Karyopharm Therapeutics Inc Newton MA

Maisonneuve Rosemont Hospital University of Montreal QC Canada

Multiple Myeloma and Amyloidosis Service Columbia University New York NY

Norton Cancer Institute St Matthews Campus Louisville KY

Princess Margaret Cancer Centre Toronto ON Canada

Queen Elizabeth 2 Health Sciences Centre and Dalhousie University Halifax NS Canada

Swedish Cancer Institute Seattle WA

University of North Carolina Chapel Hill NC

University of Rochester Rochester NY

Vancouver General Hospital Vancouver BC Canada

Vanderbilt University Medical Center Nashville TN

Weill Cornell Medicine New York NY

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ClinicalTrials.gov
NCT03110562, NCT02343042