Will PD-1/PD-L1 Inhibitor Become a True Salvage Therapy for Relapsed or Refractory Patients with Hematological Malignancies?

The treatment of cancer has evolved tremendously with the advent of immunotherapy. The effort of several groups in 1990’s led to the discovery that cancer cells use a specific mechanism called the Programmed death-1 pathway to evade the host immune response. Since then, several drugs and clinical trials have been designed that either block the receptor PD-1 or its ligand PD-L1. Recent approval of four different PD-1/PD-L1 inhibitor drugs avelumab, pembrolizumab, nivolumab and atezolizumab in different solid tumors have established PD-1 inhibition as a promising pathway in other cancers. The primary option for relapsed or refractory patients with hematological malignancies and who is ineligible to hematopoietic stem cell transplantation is chemotherapy. However, poor response, poor overall survival benefit and long term side effects seen with chemotherapy arises a dire need for identification of specific targeted therapy in these patients as well. The graft versus leukemia or lymphoma effect observed on lymphocyte infusion highlights the ability of immune response to kill cancer cells. The recent approval of nivolumab and pembrolizumab in classical Hodgkins lymphoma as well as the expression of PD-1 in several different hematological malignancies establishes PD-1 checkpoint inhibitors as a potential therapy for relapsed or refractory hematological malignancies. However, the lower response rate of PD-1 inhibitors in different hematological malignancies compared to cHL, the unique biology of cHL enabling better response in this disease group as well as the growing number of clinical trials with bispecific antibodies and chimeric antigen T-cell receptors could hinder the development of PD-1 inhibitors as the dominant salvage therapy in this relapsed or refractory hematological malignancies. In the end, the therapy that shows highest benefit will become the mainstay for salvage therapy.