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Blood. 2019 Aug 1;134(5):421-431. doi: 10.1182/blood.2019000722. Epub 2019 May 21.

Daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma.

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Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY.
Hospital 12 de Octubre, H12O-CNIO, Haematological Malignancies Clinical Research Unit, Universidad Complutense, Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain.
University Hospital of Salamanca/Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
Hôpital Bretonneau, Centre Hospitalier Régional Universitaire, Tours, France.
Institut Català d'Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Barcelona, Spain.
Hôpital Saint Louis, Paris, France.
Clinica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra, Navarra, Spain.
Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX.
University of Chicago Medical Center, Chicago, IL.
Janssen Research & Development, LLC, Leiden, The Netherlands.
Janssen Research & Development, LLC, Raritan, NJ.
Janssen Research & Development, LLC, Spring House, PA.
Winship Cancer Institute, Emory University, Atlanta, GA; and.
University Hospital Hôtel-Dieu, Nantes, France.


Patients with relapsed or refractory multiple myeloma (RRMM) have limited treatment options and poor survival outcomes. The increasing adoption of lenalidomide-based therapy for frontline treatment of multiple myeloma has resulted in a need for effective regimens for lenalidomide-refractory patients. This phase 1b study evaluated daratumumab plus carfilzomib and dexamethasone (D-Kd) in patients with RRMM after 1 to 3 prior lines of therapy, including bortezomib and an immunomodulatory drug; lenalidomide-refractory patients were eligible. Carfilzomib- and daratumumab-naïve patients (n = 85) received carfilzomib weekly on days 1, 8, and 15 of each 28-day cycle (20 mg/m2 initial dose, escalated to 70 mg/m2 thereafter) and dexamethasone (40 mg/wk). Of these, 10 patients received the first daratumumab dose as a single infusion (16 mg/kg, day 1 cycle 1), and 75 patients received a split first dose (8 mg/kg, days 1-2 cycle 1). Subsequent dosing was per the approved schedule for daratumumab. Patients received a median of 2 (range, 1-4) prior lines of therapy; 60% were lenalidomide refractory. The most common grade 3/4 treatment-emergent adverse events were thrombocytopenia (31%), lymphopenia (24%), anemia (21%), and neutropenia (21%). Infusion-related reactions were observed in 60% and 43% of single and split first-dose patients, respectively. Overall response rate was 84% (79% in lenalidomide-refractory patients). Median progression-free survival (PFS) was not reached; 12-month PFS rates were 74% for all treated patients and 65% for lenalidomide-refractory patients. D-Kd was well tolerated with low neutropenia rates, and it demonstrated deep responses and encouraging PFS, including in patients refractory to lenalidomide. The trial was registered at as #NCT01998971.

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