Pembrolizumab is a PD-1 inhibitor that blocks the interaction of PD-1 with its ligands, PD-L1/PD-L2. Studies have shown that the combination of pembrolizumab, lenalidomide, and dexamethasone may provide effective antitumor activity in patients with relapsed/refractory multiple myeloma (RRMM). The goal of this study is to evaluate the safety and efficacy of pembrolizumab plus lenalidomide and low-dose dexamethasone in patients with RRMM, as well as to determine the maximum tolerated dose in this patient population.
The KEYNOTE-023 trial is an open-label phase 1 study in which patients received intravenous pembrolizumab 200 mg every 2 weeks, oral lenalidomide 25 mg on days 1 to 21, and dexamethasone 40 mg once per week on each 28-day cycle. The primary end point was safety. Overall response rate (ORR) was assessed by International Myeloma Working Group 2006 criteria. Exploratory biomarker analyses were also included, and investigators observed flow cytometry (PD-L1, PD-L2 on CD38+CD138+ cells) at screening or predosing cycle 1, day 1 bone marrow aspirate. Patients in the study had a median age of 61 years and a median of 4 prior lines of therapy at baseline. Seventy-six percent of patients were lenalidomide refractory and 66% of patients were double refractory. For response-evaluable patients, ORR was 44% (22/50); 2 patients reported stringent complete response, 6 patients reported very good partial response, and 14 patients reported partial response. ORR was 35% (13/37) in patients who were refractory to lenalidomide and 33.3% (10/30) for patients refractory to both lenalidomide and bortezomib.
The most common grade ≥3 treatment-related adverse events (TRAEs) reported were neutropenia (32%), thrombocytopenia (16%), and anemia (8%). Two (3.2%) patients died (hepatic failure, ischemic stroke) due to TRAEs. Immune-related adverse events occurred in 8 (12.9%) patients. No pneumonitis was reported.
Pembrolizumab plus lenalidomide and low-dose dexamethasone showed an acceptable safety profile and antitumor activity in patients with RRMM. These results were also observed in patients refractory to lenalidomide and to lenalidomide and bortezomib. These results in a heavily pretreated patient population support ongoing clinical investigation.
Ocio EM, et al. ASCO Abstract 8015.
