Immunotherapy is being studied as a potential treatment modality in multiple myeloma (MM). Programmed death 1 (PD-1) receptor and its ligand (PD-L1) is one mechanism of immune evasion by MM to suppress T-cell function. This study was conducted to evaluate whether pembrolizumab, a PD-1–blocking antibody, would enhance the immunomodulatory properties of pomalidomide in heavily pretreated patients with relapsed/refractory MM.
In this phase 2 study, 48 patients with relapsed/refractory MM received 28-day cycles of pembrolizumab 200 mg intravenously every 2 weeks plus pomalidomide (4 mg daily for 21 days) and dexamethasone 40 mg weekly. The study measured safety and efficacy as well as correlation of the CD3/PD-1 on T cells and PD-L1 on plasma cells with response.
The median age of participating patients was 64 years. Patients had a median of 3 lines of prior therapy (range, 2-5). All patients had received both immunomodulatory drugs and proteasome inhibitors, and 72% had prior autologous stem-cell transplantation.
In terms of safety, the most frequently occurring hematologic toxicities (≥grade 3) included neutropenia, anemia, lymphopenia, and thrombocytopenia. The most frequently occurring nonhematologic grade ≥3 events included hyperglycemia, upper respiratory tract infections, fatigue, and rash. Pneumonitis occurred in 6 patients.
Partial response or better was observed in 29 (60%) of 48 patients, including the following: stringent complete response: n = 3, 6%; near complete response: n = 1, 2%; very good partial response (VGPR): n = 9, 19%; and partial response: n = 16, 33%. Additionally, 3 (6%) patients had minimal response, 11 (23%) had stable disease, 2 progressed, and 3 were not evaluable for response. Overall response rate results were also encouraging for double-refractory patients and patients with high-risk cytogenetics. Median duration of response for responding patients was 16.3 months; progression-free survival was 17.4 months; overall survival was not reached. Researchers concluded that the combination of pembrolizumab, pomalidomide, and dexamethasone shows promising durable therapeutic activity and an acceptable safety profile in patients with relapsed/refractory MM.
Badros AZ, et al. ASH 2016. Abstract 490.