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Blood. 2019 May 21. pii: blood.2019000722. doi: 10.1182/blood.2019000722. [Epub ahead of print]

Daratumumab Plus Carfilzomib and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma.

Author information

1
Mt Sinai, United States ajai.chari@mssm.edu.
2
Hematology Department, Hospital Universitario 12 de Octubre. Instituto de Investigacion 12 de Octubre. Univ Complutense, Spain.
3
Department of Hematology, University Hospital of Salamanca7IBSAL, Spain.
4
Hospital Clínic Universitari, IDIBAPS, Barcelona, Spain.
5
Hematology & cell therapy, CHRU TOURS, France.
6
Clinical Hematology, ICO - Hosp Germans Trias i Pujol, Spain.
7
Saint-Louis University Hospital AP-HP, Paris France., France.
8
Hematology, Clinica Universidad de Navarra, Spain.
9
Baylor Cancer Hospital, United States.
10
Medicine, University of Chicago, United States.
11
R&D, Janssen Biologics, Netherlands.
12
Biostatistics, Janssen Pharmaceuticals, United States.
13
Janssen R&D, United States.
14
Janssen Research & Development, LLC, United States.
15
Winship Cancer Institute, Emory University School of Medicine, United States.
16
Universite de Nantes, Hospital, Hematology Department, France.

Abstract

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 MM has resulted in a need for effective regimens for lenalidomide-refractory patients. This phase 1b study evaluated daratumumab plus carfilzomib and dexamethasone (DKd) in patients with RRMM after 1-3 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/week. 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 lenalidomiderefractory patients. D-Kd was well tolerated with low neutropenia rates, and demonstrated deep responses and encouraging PFS, including patients refractory to lenalidomide. The study was registered at www.clinicaltrials.gov as #NCT01998971.

PMID:
31113777
DOI:
10.1182/blood.2019000722

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