Sunday, March 5, 2017

Patients with preexisting immune disease, melanoma, and treatment with Anti-PD-1? Yes, this can be done. Yes, autoimmune flares should be treated with immunosuppressive therapy while on immunotherapy. And YES!!!! These patients can still attain a response!


Back when the world was young (2010 or so) and ipi (in other words, immunotherapy period) was finally producing positive responses for folks with melanoma, we simultaneously learned of the negative effects that could be wrought on the poor patient's immune system and really feared what could possibly happen if you were treated with immunotherapy when you KNEW that you already had an existing autoimmune disease process like asthma, colitis, or arthritis.  The solution by pharma and researchers? Exclusion from treatment!!!  By 2014, with this still unsolved conundrum hanging in the air, we certainly didn't know what to do with folks who developed immune related side effects to ipi, but still needed treatment for melanoma.  Could they be treated with the two newer immunotherapy drugs, anti-PD-1 products Nivo (Opdivo) or Pembro (Keytruda)?  No!  Exclusion from treatment remained the norm...as you can see in this post!!  (Yes, children.  Folks talked pretty funny back then, calling Keytruda, first MK-3475, then Lambrolizumab, then Pembrolizumab! Crazy things happen when the world is new!!)

Anyhow - here's the link:

Program for MK-3475 in Participants With Metastatic Melanoma Who Have Failed Standard of Care Therapy Including Ipilimumab (MK-3475-030)  which says in part, with my response:
Exclusions include - "history of life-threatening or severe immune-related adverse event" on prior immunotherapy.   Who decides?  Is an admission for colitis on ipi, though now recovered, considered a "severe immune-related adverse event"?  Is ipi induced hypothyroidism?

As things moved along...there was this:  April 2016: Anti-PD1 success in melanoma despite prexisting autoimmune disease, a case report

And this from ASCO (See the first abstract):  ASCO 2016 - Three anti-PD-1 reports

Now, there's this:

Programmed cell death protein-1 (PD-1) inhibitor therapy in patients with advanced melanoma and preexisting autoimmunity or ipilimumab-triggered autoimmunity. Gutzmer, Koop, Meier, et al. Eur J Cancer. 2017 Feb 16.


Programmed cell death protein 1 (PD-1) inhibitors are a common treatment strategy for metastatic melanoma and other tumour entities. Clinical trials usually exclude patients with preexisting autoimmune diseases, thus experience with PD-1 inhibitor (PD-1i) in this patient population is limited.
Metastatic melanoma patients with preexisting autoimmune disorders or previous ipilimumab-triggered immune-related adverse events (irAE) undergoing treatment with PD-1i from seven German skin cancer centres were evaluated retrospectively with regard to flare of the preexisting autoimmunity and development of new, not preexisting irAE as well as response to PD-1i therapy.
In total, 41 patients had either preexisting autoimmunity (n=19, group A, including two patients with additional ipilimumab-triggered autoimmune colitis) or ipilimumab-triggered irAE (n=22, group B). At PD-1i therapy initiation, six patients in group A and two patients in group B required immunosuppressive therapy. In group A, a flare of preexisting autoimmune disorders was seen in 42% of patients, new irAE in 16%. In group B, 4.5% of patients showed a flare of ipilimumab-triggered irAE and 23% new irAE. All flares of preexisting autoimmune disorders or irAE were managed by immunosuppressive and/or symptomatic therapy and did not require termination of PD-1i therapy. tumour responses (32% in group A and 45% in group B) were unrelated to occurrence of autoimmunity.
While preexisting autoimmunity commonly showed a flare during PD-1i therapy, a flare of ipilimumab-triggered irAE was rare. Response rates were above 30% and unrelated to irAE. PD-1i therapy can be considered in patients with autoimmune disorders depending on severity and activity of autoimmunity.

So....while caution and careful monitoring is certainly warranted...these peeps with an inherent pre-existing autoimmune process or one gained from having taken ipi....were successfully managed with "immunosuppressive therapy", "did not require termination of anti-PD-1 therapy", AND gained responses at a rate of 32-45%!!!!!!!!!!!!!!

ONE MORE TIME! Folks with immune disease took anti-PD-1, took prednisone or other immunosuppressive treatment to manage flares, did NOT have to stop anti-PD-1 therapy, and many DID gain a response!  

Could all you oncologists out there read and repeat??  Folks with auto-immune conditions CAN take immunotherapy with careful monitoring. Auto-immune flares SHOULD be treated with immunosuppressive therapy while on immunotherapy.  AND these patients can STILL.....GAIN A RESPONSE!  

And in case that still isn't clear enough...  What happens to folks with recurrent Stage IV melanoma who aren't effectively treated????  There ain't no Stage V people!

Okay, I'll quit yelling.  For now. - c

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