TY - JOUR T1 - Pembrolizumab, pomalidomide and low dose dexamethasone for relapsed/refractory multiple myeloma JF - Blood JO - Blood DO - 10.1182/blood-2017-03-775122 SP - blood-2017-03-775122 AU - Badros, Ashraf AU - Hyjek, Elizabeth AU - Ma, Ning AU - Lesokhin, Alexander AU - Dogan, Ahmet AU - Rapoport, Aaron P. AU - Kocoglu, Mehmet AU - Lederer, Emily AU - Philip, Sunita AU - Milliron, Todd AU - Dell, Cameron AU - Goloubeva, Olga AU - Singh, Zeba Y1 - 2017/01/01 UR - http://www.bloodjournal.org/content/early/2017/05/01/blood-2017-03-775122.abstract N2 - This is the first trial to investigate PD-1 inhibitor, pembrolizumab, and an IMiD (pomalidomide) in MM with promising clinical efficacy.PD-L1 expression on myeloma cells and PD-1 on marrow infiltrating T lymphocytes are potential biomarkers for efficacy of PD-1 blockade. Programmed death 1 (PD-1) receptor and its ligand (PD-L1) facilitate immune evasion in multiple myeloma (MM). We hypothesized that pembrolizumab, PD-1-antibody, can enhance anti-myeloma cellular immunity generated by pomalidomide leading to improved clinical responses. In this single-center, phase II study, 48 patients with relapsed/refractory MM (RRMM) received 28-days cycles of pembrolizumab, 200 mg intravenously every 2 weeks, pomalidomide 4 mg daily for 21 days and dexamethasone 40 mg weekly. Patients had a median of 3 (range: 2-5) lines of therapy, median age 64 (range: 35-83) years and had received both immune modulatory agent and proteasome inhibitor; (35 [73%] of 48) were refractory to both; (31 [70%]) had received an autologous transplant and (30 [62%]) had high-risk cytogenetics. Adverse events grade 3-4 occurred in (19 [40%] of 48 patients) including hematologic toxicities (19 [40%]), hyperglycemia (12 [25%] and pneumonia (7 [15%]). Autoimmune events included pneumonitis (6 [13%]) and hypothyroidism (5[10%]), mostly ≤ grade 2. Objective responses occurred in (29 [60%] of 48) patients including: sCR/CR (4 [8%]), VGPR (9 [19%]) and PR (16 [33%]); median duration of response was 14.7 months (95% CI 7.9-17.5). At median follow-up of 15.6 months (95% CI 9.2-17.5), progression free survival (PFS) was 17.4 months (95% CI 11.7-18.8) and overall survival was not reached (95% CI 18.9-NR). Analyses of pretreatment marrow samples revealed a trend for increased expression of PD-L1 in responding patients and longer PFS with increased T-lymphocyte infiltrates, irrespective of PD-1 expression. Pembrolizumab, pomalidomide and low-dose dexamethasone has acceptable safety and durable responses in RRMM patients. This trial was registered at www.clincialtrials.gov as # NCT02289222 ER -