BACKGROUND: Multiple myeloma (MM) patients with high cytogenetic risk have poor outcomes. In CASTOR, daratumumab plus bortezomib/dexamethasone (D-Vd) prolonged progression-free survival (PFS) versus bortezomib/dexamethasone (Vd) alone and exhibited tolerability in patients with relapsed or refractory MM (RRMM). METHODS: This subgroup analysis evaluated D-Vd versus Vd in CASTOR based on cytogenetic risk, determined using fluorescence in situ hybridization and/or karyotype testing performed locally. High-risk patients had t(4;14), t(14;16), and/or del17p abnormalities. Minimal residual disease (MRD; 10-5 sensitivity threshold) was assessed via the clonoSEQ® assay V2.0. Of the 498 patients randomized, 40 (16%) in the D-Vd group and 35 (14%) in the Vd group were categorized as high risk. RESULTS: After a median follow-up of 40.0 months, D-Vd prolonged median PFS versus Vd in patients with standard (16.6 vs 6.6 months; HR, 0.26; 95% CI, 0.19-0.37; P < 0.0001) and high (12.6 vs 6.2 months; HR, 0.41; 95% CI, 0.21-0.83; P = 0.0106) cytogenetic risk. D-Vd achieved deep responses, including higher rates of MRD negativity and sustained MRD negativity versus Vd, regardless of cytogenetic risk. The safety profile was consistent with the overall population of CASTOR. CONCLUSION: These updated data reinforce the effectiveness and tolerability of daratumumab-based regimens for RRMM, regardless of cytogenetic risk status. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02136134 . Registered 12 May 2014.

Ankara University Ankara Turkey

Clinical Department of Haematology 1st Medical Department Charles University Prague Prague Czech Republic

Department of Hematology Careggi Hospital and University of Florence Firenze Italy

Department of Hematology Oncology Chonnam National University Hwasun Hospital Hwasun Jeollanamdo South Korea

Department of Hematology Sunderbyn Hospital Luleå Sweden

Department of Internal Medicine Albert Schweitzer Hospital Dordrecht The Netherlands

Department of Internal Medicine Pusan National University Hospital Busan South Korea

Department of Medicine University of Colorado Aurora CO USA

Department of Oncology Hematology and Bone Marrow Transplantation with Section of Pneumology University Medical Center Hamburg Eppendorf Hamburg Germany

Division of Hematology Oncology Columbia University New York NY USA

Erasmus MC Rotterdam The Netherlands

Fondazione IRCCS Istituto Nazionale dei Tumori University of Milan Milan Italy

Hospital Angeles Lomas Naucalpan de Juárez y alrededores Mexico

Instituto do Cancer Hospital Mae de Deus Porto Alegre Brazil

Irmandade Da Santa Casa De Misericordia De São Paulo São Paulo Brazil

Janssen Global Scientific Affairs Horsham PA USA

Janssen Research and Development LLC Beerse Belgium

Janssen Research and Development LLC Raritan NJ USA

Janssen Research and Development LLC Spring House PA USA

László Hospital 3rd Department of Internal Medicine Semmelweis University Budapest Hungary

Malignant Haematology and Stem Cell Transplantation Service Alfred Health Monash University Melbourne Australia

Mayo Clinic Florida Jacksonville FL USA

Royal Adelaide Hospital North Terrace Adelaide Australia

Seoul St Mary's Hospital Seoul South Korea

Seràgnoli Institute of Hematology Department of Experimental Diagnostic and Specialty Medicine University of Bologna Bologna Italy

Ulsan University Hospital Ulsan South Korea

Unite de Genomique du Myelome CHU Rangueil Toulouse France

University Hospital of Salamanca IBSAL Cancer Research Center IBMCC Salamanca Spain

University Medical Center of the Johannes Gutenberg University 3rd Department of Medicine Mainz Germany

University of Melbourne St Vincent's Hospital Melbourne Australia

University of São Paulo Ribeirão Preto Brazil

Winship Cancer Institute Emory University Atlanta GA USA

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ClinicalTrials.gov
NCT02136134