Scientific publications

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

Aug 1, 2019 | Magazine: Blood

Ajai Chari  1 , Joaquín Martinez-Lopez  2 , María-Victoria Mateos  3 , Joan Bladé  4 , Lotfi Benboubker  5 , Albert Oriol  6 , Bertrand Arnulf  7 , Paula Rodriguez-Otero  8 , Luis Pineiro  9 , Andrzej Jakubowiak  10 , Carla de Boer  11 , Jianping Wang  12 , Pamela L Clemens  13 , Jon Ukropec  13 , Jordan Schecter  12 , Sagar Lonial  14 , Philippe Moreau  15


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.

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

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