Positive Tumor Response to Combined Checkpoint Inhibitors in a Patient With Refractory Alveolar Soft Part Sarcoma: A Cas

[D.ap]

Positive Tumor Response to Combined Checkpoint Inhibitors in a Patient With Refractory Alveolar Soft Part Sarcoma: A Case Report


http://ascopubs.org/doi/full/10.1200/JGO.2017.009993

[Olga]

An interesting article.
Few comments:
- since as we already know that ASPS responds to a single PD-L/L1 inhibitors, perhaps the ipilimumab was not needed at all - it adds toxicity;
- PD-L testing is not at all reliable and has no connection to a possible success;
- it looks like steroids based management of the adverse effects and a low dose steroids maintenance does not block the immune system tumor specific response - at least in some cases. Steroids are immune suppressive and there was an opinion of some oncologists that taking steroids while on PD-L drugs nullifies the treatment effect - using the PD-L drugs we take the brakes off the immune system and using steroids suppresses the immune system. But from this and other cases we can see that in some way the tumor specific immune response stays.

[D.ap]

Olga
You are so correct

“it looks like steroids based management of the adverse effects and a low dose steroids maintenance does not block the immune system tumor specific response - at least in some cases. Steroids are immune suppressive and there was an opinion of some oncologists that taking steroids while on PD-L drugs nullifies the treatment effect - using the PD-L drugs we take the brakes off the immune system and using steroids suppresses the immune system. But from this and other cases we can see that in some way the tumor specific immune response stays.”

[D.ap]

Asprin has been show to aid “super charge” immune therapy by the way of its antinflammatory means,
why not steriods ?
Both maybe needed with side effects of the immunotherapy .


http://www.cureasps.org/forum/viewtopic.php?f=3&t=1569


How corticosteroids control inflammation: Quintiles Prize Lecture 2005

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1751559

[Olga]

Deb - in general systemic steroids still interfere (suppress) the immune system functions and should be used with caution in a patient taking immune therapy drugs - the jury is still out on that one, it is a very different situation with the aspirin mode of action. In cases when the corticosteroid drugs can be applied locally - in an oral solution or ointment - it is a preferable way to avoid the systemic exposure if possible, and also to taper the systemic steroids sooner than later. There are also calls for different routes of the ICI drugs adverse effects management - they can use IL-6 or other immune components systemic inhibition similar to one that are used in the rheumatic diseases, instead of general suppressing of the immune system.
The fact that the immune response continued despite the systemic steroids use might have some different significance - may be the tumor specific response once formed exist in some patients despite the PD-L resumed block and is strong enough to stand to a systemic steroids block. It is very complicated.

[D.ap]

Olga it certainly is very complicated , indeed.
I just find that the patient , when need be ie severe side effects of immunotherapy ,can have the option of using steroids so as to not have to discontinue the ICI.

[D.ap]

From the medical article



“During the course of his treatment, the patient developed a grade 2 transaminitis after his third cycle of combination therapy. This was treated with a prednisone taper starting at 50 mg per day and temporary interruption of immunotherapy. The patient resumed therapy but continued on his taper of prednisone down to 2.5 mg per day. As the result of an increase in levels of ALT and AST, the patient’s dose of prednisone was increased to 15 mg per day. Interestingly, the patient has maintained response to therapy despite the low use of steroids.”


Learn more about Elevated transaminases

https://www.sciencedirect.com/topics/me ... nsaminases

[Olga]

I am speculating that it is (probably) important to start with no steroids and normal Lymphocyte numbers so the immune system could attack tumor initially and to get its taste - then they form the tumor specific immune response. If the immune related AE (adverse effects) appear later, and the steroids treatment is initiated, probably the memory is conserved? Steroids suppress the lymphocytes production in general but as I was reading, there are many types of them and probably not all of them are depleted in the same proportion. It looks like a tumor specific response can be formed very early in course of treatment before the IrAE srart. Then that needs to be sustained to continue.