Pd-l1 expression level and effectiveness of nivolumab

It's complicated, obtu.  Isn't that always the case with melanoma?  As I said in this post, a picture is sometimes better than explaining things with words.  Look at the picture I put in this link in the section "immunotherapy":  https://chaoticallypreciselifeloveandmelanoma.blogspot.com/2017/08/melanoma-intel-primer-for-current.html  There you can see that if you don't have PD-L1 expression on your tumor, you could argue that t-cells wouldn't be attaching themselves to it and therefore failing to kill your tumor, so you wouldn't need ANTI-PD-1 to come in and bind to that switch on the t-cell.

However, as you can see from this discussion….it it not that straight forward:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2015/09/pick-your-poison-weber-and-agarwala.html  

There, two melanoma experts discuss many things…but state specifically:

"Folks with tumors that are positive for PD-L1 respond better to anti-PD1 products.   However, many problems remain with the clarity of the test, availability of the test, consistency of results, etc.  Therefore, it is a useful…though not a predictive…marker."

"In PD-L1 positive patients: those in the combo had a 58% overall response vs 18% ORR to ipi alone.  PD-L1 negative patients: had an ORR of 55% to the combo vs 4% ORR to ipi alone."

"However, when looking at PD-L1 staining:  When positive, the difference between PFS with the ipi/nivo combo vs nivo alone is negligible. So the argument may be made to go with nivo alone…since the difference in response is minimal, but side effects are much less.  However, more definitive studies are needed."

So there is the issue of the test being valid…as well as knowing exactly what the test means.  I am not sure the data supports the decision to NOT to take anti-PD-1 (Keytruda and Opdivo) when a melanoma tumor is NOT positive for PD-L1.  Melanoma itself, and certainly its interaction in our body, is multi-faceted and one test (unfortunately) does not give us a clear cut answer.

On a more positive note…(see below…stupid spam blocker won't let me finish!!!)….

There is also this:

Mol Cancer Ther. 2015 Apr;14.  PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy.  Patel SP1, Kurzrock R2.

The resurgence of cancer immunotherapy stems from an improved understanding of the tumor microenvironment. The PD-1/PD-L1 axis is of particular interest, in light of promising data demonstrating a restoration of host immunity against tumors, with the prospect of durable remissions. Indeed, remarkable clinical responses have been seen in several different malignancies including, but not limited to, melanoma, lung, kidney, and bladder cancers. Even so, determining which patients derive benefit from PD-1/PD-L1-directed immunotherapy remains an important clinical question, particularly in light of the autoimmune toxicity of these agents. The use of PD-L1 (B7-H1) immunohistochemistry (IHC) as a predictive biomarker is confounded by multiple unresolved issues: variable detection antibodies, differing IHC cutoffs, tissue preparation, processing variability, primary versus metastatic biopsies, oncogenic versus induced PD-L1 expression, and staining of tumor versus immune cells. Emerging data suggest that patients whose tumors overexpress PD-L1 by IHC have improved clinical outcomes with anti-PD-1-directed therapy, but the presence of robust responses in some patients with low levels of expression of these markers complicates the issue of PD-L1 as an exclusionary predictive biomarker. An improved understanding of the host immune system and tumor microenvironment will better elucidate which patients derive benefit from these promising agents.

So….though this is from 2015, to my knowledge, we have neither made the test itself much more specific or valid, nor have we been able to plow through the vagaries of difference between how tumors act in the human body.  Hope this helps.  Celeste

PS  Would I still take anti-PD-1 with a low PD-L-1 expression from my tumor report?  Unless you could provide me and my melanoma a different, better, and more convincing treatment/argument….YES!

Hi Obtu.bt, just to add to what has been given from Celeste, is a link to Onclive last summer on this very topic of Pd-L1 + or negative staining of tumor and how it guides the Oncologist of the panel in making decision in their practices!!! Best Wishes!!! Ed   https://www.youtube.com/watch?v=HvB8cZj_qeI

Hi, I’m going to provide a little information and still muddy the water. Hopefully Celeste and Ed will know more. I enquired about having PD1 expression performed on my tumor. I will ask for results but I’m not positive my oncologist had it tested. 

The interesting fact I received from my oncologist was that she has patients with no PD1 expression that responded to anti PD1 immunotherapy (Keytruda or Opdivo), and patients with PD1 expression that did not respond. It seems melanoma reacts differently than NSCLC where patients with at least 50% PD1 expression respond better. I will see my oncologist in 3 weeks and see if it was completed. It’s somewhat a moot point for me because I responded, but you can still have response even without expression. I do go to one of the top cancer facilities so the information provided to me is usually pretty accurate. Hopefully others will post in with their tumors PD1 expression and response. Also, I’m on Keytruda but don’t believe that makes any difference.

Good luck,

Bill

Hi all,

Just for a bit of personal experience to muddy the waters… I have a very low expression less than 5% and my melanoma has responded very well to both Ipi and Keytruda.  So far so good no more mel.

I had the PD1 test in conjunction with a standard lung cancer protocol.  I'm not sure what the deal is, why pd1 kicked me's butt but didn't do snot for Larry the lung cancer.  I'm just figuring that they are different beasts.  

Anyway just to say that Keytruda worked well for me even though I had a very low expression of PD1.

Shalom!

Julie