Programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) engagement is a physiologic process inhibiting T cells’ overactivation and serves to maintain self-tolerance and prevent autoimmunity. Several trials have demonstrated the clinical activity of a variety of antibodies that target either PD-1 or PD-L.

Patients who experienced a relapse of diffuse large B-cell Lymphoma and Follicular Lymphoma and response rates exceeding 60% were reported in patients who experienced a Hodgkin lymphoma relapse (HL). Two naked antibodies that targeted PD-1, nivolumab and pembrolizumab, produced 87% and 66% response rates, respectively.

The next step is to combine brentuximab vedotin with PD-1/PD-L1–targeted agents. If the combination of brentuximab vedotin and PD-1/PD-L1–targeted monoclonal antibodies fails to increase the complete response rate, these agents will likely be used in sequence rather than combination.

PD-1/PD-L1 antibodies are usually combined with front-line chemotherapy regimens, like rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone and bendamustine plus rituximab. Finally, for incurable lymphomas, such as follicular and mantle cell lymphoma, incorporating PD-1/PD-L1–blocking antibodies into chemotherapy-free regimens is an obvious strategy that will need to be examined.

In summary, PD-1/PD-L1 antibodies provide an unprecedented opportunity to change the way we treat cancer, including Lymphoma.