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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 antimyeloma cellular immunity generated by pomalidomide, leading to improved clinical responses. In this single-center, phase 2 study, 48 patients with relapsed/refractory MM (RRMM) received 28-day cycles of pembrolizumab, 200 mg IV 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 an immune modulatory drug (IMiD) 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 to 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 stringent complete response/complete response (4 8%), very good partial response (9 19%), and partial response (16 33%); median duration of response was 14.7 months. At median follow-up of 15.6 months, progression-free survival (PFS) was 17.4 months and overall survival was not reached. 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 have acceptable safety and durable responses in RRMM patients. This trial was registered at www.clincialtrials.gov as #NCT02289222.
Badros et al. (Tue,) studied this question.