MSK Researchers Study Blood Biomarkers to Help Answer Questions about Why Some Patients Don't Respond to Immunotherapy

Bottom Line: Researchers from Memorial Sloan Kettering Cancer Center (MSK) and their colleagues at the University of Pennsylvania (UPenn), in collaboration with the Parker Institute for Cancer Immunotherapy (PICI), studied changes in the blood of patients with stage IV melanoma who were all treated with the PD-1 drug pembrolizumab. Researchers looked at circulating immune cells called T cells that showed signs of being “reinvigorated” by the PD-1 therapy.

The study authors found relationships between the level of reinvigoration and tumor burden, which is correlated with clinical outcome. The research, published in Nature, is the first major study to come from PICI, of which MSK and UPenn are both founding members. Launched in April 2016, PICI was founded by Sean Parker and is led by University of California, San Francisco immunologist Jeffrey Bluestone.

Journal: “T-cell invigoration to Tumor Burden Ratio Associated with Anti-PD-1 Response” appears in the April 10, 2017, issue of Nature.

Authors: The study was led by UPenn in collaboration with MSK’s Michael Postow, MD; Jedd Wolchok, MD, PhD; Katherine Panageas, DrPH; Philip Wong, PhD; and Matthew Adamow.

Background:  Researchers found that blood can be an important source of information relevant to understanding a patient’s response (or lack of response) to immunotherapy. Researchers from both MSK and UPenn studied the changes in the blood of 47 patients — 18 from MSK and 29 from UPenn — with stage IV melanoma who were all treated with the PD-1-blocking drug pembrolizumab. Researchers analyzed circulating immune cells called T cells that showed signs of being “reinvigorated” by the PD-1 therapy.

Findings: The study authors found relationships between the level of reinvigoration and tumor burden, which is correlated with clinical outcome. Researchers also suggest that this on-treatment biomarker, when factored in along with other prognostic indictors, could one day provide clinicians with a way to determine whether an immunotherapy treatment is working for a particular patient or whether it might be time to try a different therapy.   

Method: No statistical methods were used to predetermine sample size and experiments were not randomized. Investigators were not blinded to allocation during experiments and outcome assessment. MSK researchers collected samples from patients that were treated in this early-phase clinical study and were banked in MSK’s immune monitoring facility. Tumor burden was then assessed by the researchers.

Author Comments:  “The idea is that there is a relationship between the reinvigoration of the immune system and the amount of tumor that the patient is facing,” explained Michael Postow, a medical oncologist at MSK and author on the paper, who was also involved in the phase I clinical trial at MSK from which a portion of the patients on this study were taken. “So if a patient has a small amount of tumor and a lot of reinvigoration, they are likely to do well. If the patient has poor reinvigoration and a lot of tumor, they are unlikely to do well — at least with PD-1-blocking drugs alone.”

“This research helps to answer some of the critical questions around why some patients don’t respond to anti-PD1 inhibitors and some do,” said Jedd Wolchok, Chief of the Immunotherapuetics Service and Director of the PICI at MSK. “We wanted to understand what was happening to the immune system of patients that were treated with PD‑1 antibody and to characterize the immunologic changes that were happening in patients through analyzing two entirely distinct data sets. Our collaboration with our colleagues at the University of Pennsylvania was invaluable. This study is really emblematic of what Sean Parker and Jeff Bluestone envisioned when they created the Parker Institute for Cancer Immunotherapy.”