Sunday, February 11, 2018

For Jubes...and the rest of us!!! An anti-rheumatic drug that increases the effect of vemurafenib and selumetinib????


The minute B found this article he was yelling, "Oh, this might be important to Jubes!!!"  Well, I hope not!!!  Many (actually - probably most!!!) folks who take immunotherapy deal with some amount of arthralgias (joint pain).  However, my sweet Anne-Louise dealt with significant arthritis/spondylitis due to her immunotherapy treatment for melanoma!  However, after prednisone and other meds like infliximab she got her joint pain under control and threw melanoma to the curb!!  But....immune disease and side effects with immunotherapy remain a significant double decker problem. 

First....what if you already know you have an immune disease like rheumatoid arthritis?  Can you still take immunotherapy?  The short answer is YES!!!  You can!!  Here is a recent post on the subject with more links within:  Immunotherapy for melanoma with a pre-existing autoimmune disease??? YES!!! You can!
Here's another report:  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!

Second...there are the folks who didn't have arthritis or other autoimmune diseases (that they knew of) at the start of treatment...but end up with all sorts of immune related side effects caused by their immunotherapy.  What should we do with them????  Treat them!  Sometimes with a break of their immunotherapy, but with prednisone and other drugs as needed.  Right then, right there!  And, YES!!!  They can still go on to have a response and rid themselves of melanoma in the process!  (Just like Jubes!!!)  Here are related posts:  One more time: Immunosuppressive therapy to manage side effects to immunotherapy does NOT affect response! New report.
And this:  Immune related side effects from immunotherapy can and SHOULD be treated!!!!
And this:  Side effects and how to manage them in targeted and immunotherapy for melanoma
And finally...this post with a treatment algorithm for neuro side effects and links to algorithms for other immune related side effects:  Neurologic side effects to immunotherapy with treatment algorithm

Okay!  You'd probably like me to get to a point!  What if there was a drug that helped folks with their rheumatic disease AND helped get rid of their melanoma????  Well now, there's this:

The anti-rheumatic drug, leflunomide, synergizes with MEK inhibition to suppress melanoma growth. Hanson, Robinson, Al-Yousuf, et al.  Oncotarget. 2017 Dec 17.  

Cutaneous melanoma, which develops from the pigment producing cells called melanocytes, is the most deadly form of skin cancer. Unlike the majority of other cancers, the incidence rates of melanoma are still on the rise and the treatment options currently available are being hindered by resistance, limited response rates and adverse toxicity. We have previously shown that an FDA approved drug leflunomide, used for rheumatoid arthritis (RA), also holds potential therapeutic value in treating melanoma especially if used in combination with the mutant BRAF inhibitor, vemurafenib. We have further characterized the function of leflunomide and show that the drug reduces the number of viable cells in both wild-type and BRAFV600E mutant melanoma cell lines. Further experiments have revealed leflunomide reduces cell proliferation and causes cells to arrest in G1 of the cell cycle. Cell death assays show leflunomide causes apoptosis at treatment concentrations of 25 and 50 µM. To determine if leflunomide could be used combinatorialy with other anti-melanoma drugs, it was tested in combination with the MEK inhibitor, selumetinib. This combination showed a synergistic effect in the cell lines tested. This drug combination led to an enhanced decrease in tumor size when tested in vivo compared to either drug alone, demonstrating its potential as a novel combinatorial therapy for melanoma.  

In this study, researchers say that leflunomide...a drug used to treat rheumatoid arthritis...seemed to have "therapeutic value" when it was combined with vemurafenib (a BRAF inhibitor) as well as when it was combined with selumetinib (a MEK inhibitor)...in both BRAF positive and BRAF wild type patients!  So far, it seems that this is in petri dishes and real live furry ratties.  However, if this works this could be super cool for getting rid of melanoma as well as a boon for folks already dealing with arthritis...or perhaps debilitated by arthralgias due to their melanoma treatment.  

It's got a ways to go before we can get too excited.  But, I like the direction!!!  As for my dear Anne-Louise....I hope that she NEVER needs another melanoma or arthritis treatment....EVER!!!!  And...I do hope to hear her play her fiddle someday!!! 

Hang in there, ratties!  (Those that are furry and those who are not so much!) - c

6 comments:

  1. My husband has had 2 hip replacements. He will soon receive the 4th opdivo/yervoy combo treatment. After he began treatment, he started having severe pain around each hip replacement, but not in any other of his joints. I wonder if the immunotherapy drugs see those devices as foreign objects to be attacked? Based on symptoms, he seems to be having very positive results. Any thoughts on where I might find information about this reaction?

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  2. You can use many search engines to search for scientific articles. However, in covering immunotherapy and melanoma for many, many years, I have not seen any reports that indicate patients with joint replacements suffer any additional untoward effects from immunotherapy beyond what is usual for most.

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  3. Same thing happened to me, first when I started chemo and again when I started immunotherapy. Stretching exercises fixed it the first time, hope it works this time as well. I had one hip replacement and that's where the pain is.

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  4. Goodness. That's crazy! But in the words of Dr. Weber, "This stuff is weird!" We are still in a place where we don't know what we don't know! Hope you get better soon, Mark!!!

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    1. Exercises did not help but prednisone took away the pain.

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    2. Glad you got some relief!! Hope it is maintained when you are off prednisone!! Hang tough!

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