Anti-PD-1 Therapy May Benefit Patients with Hematologic Malignancies

March 6, 2018

Researchers report that PD-1/PD-L1 monoclonal blocking antibody allows T cells to remain active and fight malignant evolution, subsequently preventing tumor resistance.

Anti-PD-1 antibody therapy enhances eradication of refractory Hodgkin lymphoma (HL), and when used in combination with other agents may help improve outcomes for leukemia patients, according to a report in the journal Leukemia Research. Italian and American researchers report that the PD-1 (programmed cell death protein 1)/PD-L1 (ligand 1) axis is a key player in immune surveillance in hematologic malignances.

The researchers analyzed the expression of PD-L1 on malignant cells in lymphoproliferative disorders and how it contributes to malignant cell proliferation. They report that the use of PD-1/PD-L1 monoclonal blocking antibody allows T cells to remain active and fight malignant evolution. Subsequently, this prevents tumor resistance.

“The study of PD-1/PD-L1 axis in hematologic malignancies highlighted the importance of immune surveillance to cure these diseases. The use of these chemo-free drugs allowed us to obtain good results in relapse/refractory setting, in particular in Hodgkin disease, with a good toxicity profile,” said lead study author Ombretta Annibali, MD, PhD, who is with the Department of Hematology at University Campus Bio-Medico in Rome, Italy.

In terms of pathology, there is a need for standardization of the immunohistochemical testing for PD-L1 in tissue specimens from patients with lymphoproliferative disorders, according to the researchers. They believe this is critical for evaluating the results from clinical trials and for understanding just how PD-L1 expression on tumor cells actually contributes to tumor resistance.

The researchers noted that initial clinical trial data have been validated in larger phase II trials in the setting of relapsed/refractory HL, non-Hodgkin’s lymphoma (NHL), and multiple myeloma (MM). “The surprising result was embodied by checkpoint expression in extramedullary myeloma showing that these lesions are able to reproduce their environment out of the bone,” said study co-author Alba Grifoni, PhD, from the Division of Vaccine Discovery at La Jolla Institute for Allergy and Immunology in La Jolla, California.

Dr. Grifoni said clinical practice in the setting of relapsed/refractory HL, NHL, and MM is rapidly changing. It is hoped that combining PD-1/PD-L1 monoclonal antibodies with standard chemotherapies or novel hematologic agents may help improve outcomes. “In the future, new agents direct against other members of the tumor’s immune-escape activity are expected to completely restore the antitumor power of the immune system cells. These therapies have opened a new era,” Dr. Grifoni told Cancer Network.

Dr. Annibali said it is important that clinicians are aware that the PD-1/PD-L1 axis is crucial in hematologic diseases, which until now had not been fully recognized.  She said new combination therapies with anti-PD-1 antibody therapy could be in clinic relatively soon. “I believe that these agents will play an important role in the cure of lymproliferative disease. The results of ongoing clinical trials will allow us to change our clinical practice in the near future,” Dr. Annibali told Cancer Network.