Increasing evidence implicates programmed death-1 (PD-1) and its ligand (PD-L1) in antimyeloma immune suppression, with components of this pathway aberrantly expressed on myeloma cells and in the bone marrow microenvironment.1,2 Moreover, inhibition of the PD-1/PD-L1 pathway synergistically interacts with immunomodulatory drugs (IMiDs) to produce enhanced antimyeloma immune responses.3 An ongoing phase 2 study is evaluating the anti–PD-1 monoclonal antibody pembrolizumab in combination with the new-generation IMiD pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). Badros and colleagues reported on the findings of this study.4 The 24 patients enrolled in this study received 28-day cycles of pembrolizumab (200 mg intravenously) every 2 weeks plus pomalidomide (4 mg orally daily, 21 days) and dexamethasone (40 mg weekly). In this heavily pretreated cohort (median: ?3 prior therapies), all patients had received both IMiDs and proteasome inhibitors, and 70% were double refractory to both drug classes. High-risk cytogenetics were observed in 42% of the patients. Grade 3/4 hematologic adverse events (AEs) included neutropenia (29%), lymphopenia (17%), and thrombocytopenia (8%); nonhematologic grade 3/4 AEs included fatigue (n = 1), dyspnea (n = 2), infection (n = 3), palpitation (n = 1), and rash (n = 1). Immune-related AEs of clinical significance included hypothyroidism (all grades), hepatitis (3% grade 3/4), and pneumonitis (3% grade 3/4). Five patients had pomalidomide dose reductions due to rash, neutropenia, palpitations, and fatigue. Two patients died; 1 due to progressive disease and 1 due to sepsis. Overall, 16 of the 27 evaluable patients (60%) achieved responses, 1 with stringent complete response, 4 with very good partial response, and 11 with partial response. Treatment discontinuation was mainly due to disease progression (n = 3). The authors concluded that this novel combination of pembrolizumab plus pomalidomide/dexamethasone has promising therapeutic activity and a predictable and acceptable safety profile in heavily treated patients with RRMM. The role of PD-L1 as a biomarker for this treatment regimen is under investigation.
