Looking for options for immune checkpoint inhihibitor resistance

@r123, can you help untangle the acronyms for me? Are you referring to immune checkpoint inhibitors (ICI) in the treatment of renal cell carcinoma?

Yes, immune checkpoint inhibitors in any cancer. There are more and more of us who will receive a pd-1 immunotherapy agent as first line...and will need solutions when they fail, flag, or when our maintenance period ends. I'm my case, signatera went up during pd1 maintenance, we identified a likely lymph node, did a course of sbrt and the radiation seems to jump start the immunotherapy...there are many immunotherapy+ chemo first line options...wondering if other patients have experience with their medical team salvaging exhausted immune systems further down the line

@r123, thanks for elaborating. Good question. I'll bring @joancarol @val64 @mmatunis @jaxfl @davidwrenn @grammato3 into this discussion as they may have something to add.

I found this paper:
- Resistance mechanisms to immune checkpoint inhibitors: updated insights https://link.springer.com/article/10.1186/s12943-024-02212-7

Abstract:
"The last decade has witnessed unprecedented succusses with the use of immune checkpoint inhibitors in treating cancer. Nevertheless, the proportion of patients who respond favorably to the treatment remained rather modest, partially due to treatment resistance. This has fueled a wave of research into potential mechanisms of resistance to immune checkpoint inhibitors which can be classified into primary resistance or acquired resistance after an initial response. In the current review, we summarize what is known so far about the mechanisms of resistance in terms of being tumor-intrinsic or tumor-extrinsic taking into account the multimodal crosstalk between the tumor, immune system compartment and other host-related factors."

Am I understanding correctly, that pinpointing the lymph node as the point of resistance, you were able to continue treatment with immunotherapy + chemo after a raditation?

@colleenyoung and @r123: I appreciate your tracking down that journal paper, Colleen, but it was very scientifically dense even to me with a medical background to fully digest. Unlike @rls, I have not been resistent to ICI as it was quite effective in a relatively short time in completely resolving my metastatic melanoma lung nodule. However, the treatment plan was that I was to remain on Keytruda for a full two years to achieve maxium effectiveness. Unfortunately, due to a significant adverse reaction that was confirmed to be linked to the ICI this past week in a GI biopsy, there is potential I may need to discontinue this line of treatment indefinitely. And more aggressive immunotherapy would only worsen the symptoms I experienced. I do have many concerns about this and am anxious to discuss how this will impact my care plan when I meet with my oncologist on Monday.

I will respond when I know more and am anxious to hear what other contributors have to say.