Programming the immune checkpoint to treat hematologic malignancies

Abstract

Introduction: Hematologic malignancies manipulate the immune suppressive pathways involving CTLA-4, PD-1, and others to promote immune tolerance of cancer. New monoclonal antibodies targeting immune checkpoints are showing meaningful responses in the treatment of relapsed and refractory Hodgkin lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia. The basis for success of anti-PD-1 therapy appears to be expression of PD-L1 on tumor cells and cells of the tumor microenvironment (TME). While adverse events associated with immune checkpoint inhibitors are capable of generating auto-immune phenomena, in general these therapies are well tolerated.

Areas covered: In this review, the authors discuss the development of immune checkpoint inhibitors and activators which hold promise as useful therapies in malignancies of hematologic origin, since many exploit endogenous pathways to induce tolerance. By programming the immune response to attack hematologic malignancies, unique regimens can be developed to optimally treat patients with curative potential.

Expert opinion: The utilization of immune checkpoint targeting agents to boost the innate and acquired immune systems to eradicate human malignancies represents a unique opportunity to develop novel therapies with increased clinical efficacy. Side effects of these therapies come with the price of auto-immune phenomena that require appropriate management.

Keywords: CTLA-4; Hematologic malignancy; PD-1; PD-L1; immune checkpoint inhibitors and activators; immune related adverse events; leukemia; lymphoma; multiple myeloma; myelodysplastic syndromes.