The only significant correlative finding from the study was that a very low baseline, sPD-1 or absence of a very high PD-1 at week 0, followed by a decline in sPD-1 at week 5, was predictive of surviving 3 of more years after treatment with DCV, but not TCV. These criteria were able to correctly classify 8 of 10 patients who survived 3 years or more and 6 of 7 patients who did not survive 3 years.
“These are 2 wildly different biological situations that they’ve had to combine to get statistically relevant results. You need to get a bigger enough data set to tease these 2 groups apart,” said Dr Bartee.
Despite the lower numbers of patients involved, the biological reasoning for the responses seen and presented in the paper is likely to have some merit.
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“This suggests to me that patients with no sPD-1 haven’t really recognized the tumor as foreign and activated an immune response. Biologically this makes sense, and these are patients that even if you hit them hard with immune checkpoint inhibition, they still don’t respond, as they haven’t recognized the tumor,” said Elizabeth Buchbinder, MD, a medical oncologist who focuses on melanoma at the Dana-Farber Cancer Institute in Boston, Massachusetts.
The paper also proposes that high sPD-1 levels at week 0 could be a sign of a blunted, ineffective immune response, much similar to increased PD-1 expression on the surface of T cells, which is a well-described indicator of T-cell exhaustion.
The majority of new research looking at PD-1 expression on T cells also concurrently looks for levels of PD-L1 on the tumor being targeted, but this particular study did not include this analysis.
“We were not able to look at PD-L1 — the permissions of the reference laboratory could not test for it. But based on other literature, in general, the 2 [PD-1 and PD-L1] seem to move in the same direction. Most likely the patients with low levels of PD-1 probably had undetectable levels of PD-L1 and conversely, similar,” said Dr Dillman, adding that he believed there was a good chance that the proteins were complexed together.
