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

Abstract

K E Y P O I N T S l Daratumumab plus carfilzomib/ dexamethasone induced deep durable responses, regardless of prior treatment with lenalidomide. l Splitting the first dose of daratumumab was feasible, and the regimen was well tolerated.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; lenalidomiderefractory patients were eligible. Carfilzomib-and daratumumab-naïve patients (n 5 85) received carfilzomib weekly on days 1, 8, and 15 of each 28-day cycle (20 mg/m 2 initial dose, escalated to 70 mg/m 2 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.

Daratumumab in high‐risk relapsed/refractory multiple myeloma patients: adverse effect of chromosome 1q21 gain/amplification and GEP70 status on outcome

“…Based on these studies, daratumumab monotherapy and combinations are FDA‐approved in RRMM. Daratumumab in combination with carfilzomib/dexamethasone( D‐Kd) showed an overall response rate (ORR) of 79% with a complete remisson (CR) rate of ≥29% in the lenalidomide‐refractory RRMM and is encouraging with increasing numbers of patients exposed to lenalidomide during induction therapy (Chari et al , ). However, the efficacy of daratumumab has been variable in these studies with the best results seen in patients with fewer lines of therapy.…”

The Anti-CD38 Antibody Therapy in Multiple Myeloma

“…In a phase I study, 85 RRMM patients, after 1 to 3 prior lines of therapy, carfilzomib-and daratumumab-naive were treated with D-Kd (daratumumab, carfilzomib, and dexamethasone). Using this combination, 84% of patients obtained an ORR with 13% and 47% in sCR/CR and VGPR, respectively [11]. At 12 months, the PFS rate was 74% and the median PFS was not reached.…”

Proteasome Inhibitors for the Treatment of Multiple Myeloma

“…As a result, the effective regimens for lenalidomide-refractory patients are needed. A phase Ib study evaluating daratumumab plus carfilzomib and dexamethasone (DKd) in patients with relapsed or refractory MM was reported [64]. In this study, eighty-five patients who did not receive carfilzomib and daratumumab were enrolled.…”