Patients with relapsed or refractory multiple myeloma (RRMM) have limited treatments and poor survival outcomes. The growing adoption of lenalidomide-based therapy for frontline management of multiple myeloma has led to an excuse for effective regimens for lenalidomide-refractory patients. This phase 1b study evaluated daratumumab plus carfilzomib and dexamethasone (D-Kd) in patients with RRMM after one to three prior lines of therapy, including bortezomib as well as an immunomodulatory drug lenalidomide-refractory patients were qualified. Carfilzomib- and daratumumab-na?ve patients (n = 85) received carfilzomib weekly on days 1, 8, and 15 of every 28-day cycle (20 mg/m2 initial dose, escalated to 70 mg/m2 after that) and dexamethasone (40 mg/wk). Of those, 10 patients received the very first daratumumab dose like a single infusion (16 mg/kg, first day cycle 1), and 75 patients received a split first dose (8 mg/kg, days 1-2 cycle 1). Subsequent dosing was per the approved agenda for daratumumab. Patients received an average of two (range, 1-4) prior lines of therapy 60% were lenalidomide refractory. The most typical grade 3/4 treatment-emergent adverse occasions were thrombocytopenia (31%), lymphopenia (24%), anemia (21%), and neutropenia (21%). Infusion-related reactions were noticed in 60% and 43% of single and split first-dose patients, correspondingly. Overall response rate was 84% (79% in lenalidomide-refractory patients). Median progression-free survival (PFS) wasn’t arrived at 12-month PFS rates were 74% for those treated patients and 65% for lenalidomide-refractory patients. D-Kd was well tolerated with low neutropenia rates, also it shown deep responses and inspiring PFS, including in patients refractory to lenalidomide.