PMR due to immunotherapy for cancer.

I learned one of my early lessons on steroids from my wife. She has GBM. Brain swelling is just not an option. They gave her Dexamethasone for the surgery and through radiation and chemo. Then they needed her to taper off to do immunotherapy treatments. They told us as close to off as she could get. I quickly found out how difficult that might be. We could only get down to 1mg which is about the equivalent of 5.5 prednisone. Otherwise your defeating the purpose of immuno drugs. In our case avastin and keytruda. I think we did 3 infusions and then stopped due to an infection. Was the infection from the steroid use or the immuno drugs or something else. Not sure. The immuno drugs have the risk of increasing infections. This can be made much more serious by steroids. The infection was the game changer in her cancer journey. We never fully recovered. I ended up with PMR she did not have it . I cant imagine your having to deal with cancer and the PMR. I dont have an answer to give you. But in my wifes case, she was not a candidate for any more immuno treatments.

Tuckerp, Thanks for your quick reply and sharing your wife's experience. I couldn't tell from your note if she is still alive, but it seems like she went through the ringer. When I hear other peoples' stories it make me feel lucky.
As to my experience with PMR I feel terrible every morning, but by 11:00am much better and by evening I feel normal. I just need to suck it up and deal with the mornings as best I can so that I can stay on the immunotherapy.
Your story and mine are examples that every drug has side effects and it's all about balancing the risks and benefits and then being brave when a disappointment comes along.

Yes your right. Any drug or even supplements have an effect. We have become a society of treating the symptoms not the cause. They gave my wife 6 months. That was 4 years ago. She is on hospice. We deal with one day at a time.

I have "PMR" due to Keytruda treatment for melanoma. I would like to hear from anyone with this "immune related adverse effect". I put PMR in quotes because my version of PMR is not the usual bursitis inflammation but rather inflammation of those same pelvic and pectoral girdle muscles surrounding the usually inflamed joints: femur adductors, glutes, hamstring muscles and [not so much] pectoral musculature. Probably this is some type of myofasciatis. To be clear, I have no joint pain; ie, no pain with passive movement of a limb. I've had no loss of strength, only pain upon muscle contraction. [There are some small clinical studies using MRI describing my, myofasciatus, version of PMR]. Rheumatologists automatically assume I have RA. Wrong. For me, soon after Keytruda treatment any antigenic challenge caused this muscle pain. Later, major PMR-like symptoms had a sudden onset with a case of sciatica: I couldn't even turn over in bed, and I went on 15 mg prednisone per day. As I tapered down from the prednisone, due to my loss of agility I tripped and fractured 3 bones. That made the PMR worse, and I had to go back up to 15 mg prednisone per day. Accompanying the muscle contraction pain, I have what some call "autoimmune fatigue". That is now helped with daily doses of Modafinil. Now, almost 3 years later I am off daily prednisone. But even putting on my socks is still a challenge, and I still have resurgences of PMR. Resurgences require temporary prednisone courses. In between the resurgences, the ongoing fatigue and weakness continues. That is, I'm not back to "normal": mornings are always slow, and I cannot do more than about 2 hr easy physical work in the afternoons. My university med sch oncologist understands all this; other physicians, including rheumatologists, nope. Anyone with an experience similar to this and care to comment?

@reaton1indracom
My story is very similar to yours. Immunotherapy for metastatic melanoma which was working great until the PMR started. High dose prednisone (20mg per day) which the oncologist wanted to have me wean down to 10mg per day before starting my treatments back up. Basically we worked at getting down to the 10mg, but I couldn't tolerate that low dose. (I have never gone back on the immunotherapy- my oncologist says that my body is telling me that it has had enough). I am now working with a rheumatologist working on a taper again. It's very frustrating.
I will try to think of any hints I could give you. Unfortunetly I had a brain met that bled so my writing skills aren't great. I am thrilled to still be able to read.

@elizabethvalerie, @reaton1indracom - I'm wondering if this post by Mike @dadcue in another PMR discussion might explain what you might also be experiencing with the prednisone tapering - https://connect.mayoclinic.org/comment/1574242/.

@johnbishop

It is so difficult to know what to do. I’m facing the same problem because now I have cancer. I don’t know what to do. A surgeon says surgery might be a cure but I would need to stop my biologic treatment for a couple of months.

I don’t have any symptoms of cancer. Mine is slow growing but it could cause some problems in the future. I’m so afraid of surgery because it will remove parts of my abdominal organs. The surgeon says the cancer has been there for at least 6 years. It bothers me that suppressing my immune system can cause cancer. It is a rare type of cancer so nobody knows what causes it.

Ironically … just a few months ago before I knew about the cancer … I told my rheumatologist that I was having more pain than usual. The dose of my biologic was increased but now I’m thinking that maybe wasn’t such a good idea. Now I’m reading that IL-6 inhibitors sometimes helps with the inflammation caused by my type of cancer.

@reaton1indracom I found your post very interesting. I am not sure my experience relates but I am giving it a lot of thought. I was on Keytruda in 2019-2020 for lung cancer. When it stopped working I was put on a more aggressive chemo. It worked, tumor gone, and has not returned--sort of a miracle I think. I have heard Keytruda continues to work even after treatment--which is positive. I was diagnosed with PMR 14 months ago, although I had symptoms for months before. That seems like a long time between Keytruda and PMR but maybe my PMR was present earlier. My pain is in the muscles in my shoulders, particularly the top which seems strange. Stretching with resistance bands helps a lot. My other pain is in the upper back of my legs--hamstring and gluts. It is painful to walk up stairs. This pain in harder to work on even with exercises I got from a physical therapist. It is definitely muscle pain and not joint. Mornings are bad. Even before I get out of bed I am in pain. After I get up the pain starts to go away and by mid afternoon I feel normal (except for stairs) Sitting is my enemy but it is not easy at age 78 to move constantly, I also experience fatigue. I have been tapering off prednisone and am now trying zero. I was at 1mg every other day and don't think it was making a difference. This week will be my first without any. I take Tylenol. I have an appointment with my oncologist in a couple of weeks. I have the highest regard for his expertise and will ask him what he thinks about the Keytruda connection. Until then I will keep moving and not make any plans for my mornings.

Mike @dadcue - Not sure what I would do given the same situation. I’m afraid to have surgery myself and I can’t begin to imagine how difficult it is for you.

@csimmonds

Thank you for your most thoughtful and detailed reply to my posting.

1) Likewise, my response to Keytruda was miraculous ... going from Stage 4 melanoma [and 2 surgeries] to no tumors in 4 months. Clinical studies show that people with strong irAEs [maybe 40%], tend to also not get a return of the cancer.

2) Interesting similarity between your PMR and mine. Initially I had the shoulder muscles affected as well as those of my hips. And, our cases involve the muscles themselves, rather than the joints. I have trouble going down stairs, so somewhat different hip-leg muscles affected but the same group. I find it is curious that the muscles affected control the joints that are usually inflamed by PMR.

3) Yes, mornings are bad too for me: I believe immune inflammation [eg cytokines & IL-6] increases at night during sleep. I have much better afternoons. For rough spots I use Advil in deference to prednisone if possible.

4) Re the duration of the "Keytruda connection" I don't know what you know, so please pardon these details. There are several suspected mechanisms for the development of irAEs that persist long after Keytruda ["ICI" or PD-1 inhibitor] is gone. For example, self-sustaining immune "memory", "epitope spreading" where the immune attack widens its focus, unmasked previous autoimmunity, etc.

5) If you or you oncologist are interested, or don't realize it, there are excellent published studies by a research group headed by DB Johnson, Dept of Hematology/Oncology, Vanderbilt Univ Med Ctr. I can provide references if wanted.

6) In my case PMR struck a previously healed rotator cuff injury, that is a tendon. I didn't do anything to trigger that; it just started hurting so much that they did an MRI of my shoulder to make sure it wasn't something else. And my PMR surged when I fractured 3 bones. The hypothesis is that immune activation for the healing did not turn off properly when the bones were repaired [perhaps some "self-sustaining" immunological response?]

I hope anything I've said is beneficial. Thanks again for your comments. RCE