CAR-T cell Therapy: Joint and muscle pain

Hello Greg – I underwent Car T therapy in 2018, I am currently 68 years old. The therapy was a total god send for me. My oncologist has told me that I am totally immune compromised and that is the way it will be for me, this can only be mitigated with IVIG infusions which I struggle with, as a result I have not have had and infusion to boost my immunity for more that 2 years. I have had countless aches and pains much like your wife is experiencing, I have been able to mitigate them by changing my diet, practicing a rigorous stretching routine that I have implemented. Even with that, I still experience muscle spasms, and neuropathy quit regularly. It took at least 3 years for me to get the joint pain and spasms under control. I have been fortunate in that I was able to get to this stage without any medication. My experience has been is that there is no magic fix for me. (Saying that, Car T was a magic fix) take care.

Ann, yeah, sounds like you've had a rough go of it but are slowly improving. While not good to hear that this could go on for a while, it's good knowing we're not alone in our struggles and are otherwise clear of disease for the time being. Thanks.

I was devoid of most of my energy after CAR-T for about 6-8- weeks. Very low BP and could not sit upright no longer than 20-30 minutes. My bursa sacs in my hips flared up for a while and was very painful. The left side still flares up on occasion. I ice and take anti inflammatory OTC pills. Seems to help. Once I started to recover, my energy came back quickly. It's been 11 months since CAR-T and I still mask up. We stayed cooped up for a long while and I got special accommodations at work to be in a office instead of out in open. I still take all safety precautions and we go out to eat earlier than normal. Hope your wife continues to improve.

Ann, thank you very much for sharing. She had the Polatuzamab Ruxience as a bridging immunotherapy before her CAR-T and which worked very well but is just not sustainable with aggressive or refractory DLBCL that she also has. My wife's aches and pains seem more to be joint and muscular in the hips and especially shoulders. Her 100 day PET/CT showed activity in the right hip area which wasn't presenting any discomfort at the time whereas as other painful areas did not light up. My understanding would be that inflammation can light up on a PET/CT as those areas can absorb the FDG readily as do clustering cancer cells. Follow-up MRI of the right hip was reported as a 'tear' but subsequent review by an Orthopedic specialist showed it was more like a strain or pull than anything torn. Shoulder pain wasn't bad then but then worsened and another trip to the Orthopedist who took an x-ray and determined no joint or bone issues and through manipulation was inclined to think it might be a rotator cuff issue. We've seen others report the joint/muscular issues as having been diagnosed as rotator cuff issues and such. Would need an MRI to confirm but since her immune system is compromised, surgery at this early stage would not be wise so he wasn't inclined to push doing the MRI yet and instead provided PT exercises she could do to strengthen the muscles and suggested a cortocosteroid shot as an interim therapy. She had the shot yesterday and we're waiting to see if it kicks in any relief. In the meantime, while most of her labs were trending in the right direct and in many cases now normal except for WBC and neutrophils which have been hovering around 1.4-1.6 and .6-.9 (or 600-900 depending on how one characterizes them) respectfully, a lot took a pretty good hit this week. She's been dealing with periodic bouts of what I'd describe as GI storms so along with the joint and muscle issues, probably all inflammatory in nature with the WBC and neutrophils and overall immune system still trying to figure itself out. They harvested a nice crop of T cells and apparently had a good batch of CAR-T cells they put back into her. Maybe they were too good and plentiful and having gone into CAR-T with a very low tumor burden, they are running amuck. Her doctors are not inclined to introduce any colony growth stimulating factors as her levels are not real severe and here IgG is holding it's own for now so she's not in need of any IVIG treatment. Of course, all these things are lingering and so stress and anxiety levels are over the top which doesn't help one's immune system or tendency for inflammation. Fortunately, no other immune system flare-ups like you've experienced but the tonic water idea is interesting. At this point, we're experimenting with all kinds of ways of easing inflammation both pharmacological but also dietary as she seems to be caught in a vicious cycle of being immune compromised, prone to inflammatory issues, and
exhibiting uncooperative blood levels. So breaking one of them or reducing their influence might be enough to give her body a chance to fight back better. Otherwise, she's got great energy and able to do most of what she did before CAR-T just is somewhat living in an isolated bubble with a lot of discomfort.

Greg — I certainly can sympathize with your wife's leg cramps. I started have leg/foot cramps about 3-4 months out from CAR-T, received CAR-T 12/28/22. They can be quite painful. My WBC has not recovered fully, I'm usually between 3.0-3.8. I'll be surprised if I ever reach 4.0, my oncologist is not concerned and says my immune will not be as robust as others. He says the neutrophils are more important. After several short acting injections to boost my neutrophils I was given 2 or 3 longer lasting injections and those seemed to do the job at raising them to a healthier level. I should mention before CAR-T I had to have a round of Polatuzmab, a chemo, to push back the aggressive DLBCL so that I could make it to prep for CAR-T. Luckily they were able to get enough healthy cells. I am on daily Valtrex for shingles and an anti fungal 3x a week, both for a year. I did have a breakthrough singles attack, i think because it was a very stressful time at work. My dermatologist put me on a gram of Valtrex and Gabapentin daily, my shingles was not clearing up and itching all the time. Derm said damaged nerves. Since I've been on Gabapentin I have not had any severe cramping. When I do feel the mild cramping in my feet i drink tonic water with quinine. It seems to help. What would keep me awake or have non restful sleep was the bubbly sensation in my lower legs. Most of the time I could feel a charlie horse coming on so I would immediately stand and stretch. I have not found exercise helpful.

Thanks for responding. Her neutropenia is not severe with Neutrophils running in recent months in the range of 600 to 900 and once at 1100 since having CAR-T on 6/26/23. WBC is fluctuating around 1.4 to1 .6 or so in recent months. While all 3 of her oncologists (original diagnosis and treatment oncologist where we summer, local oncologist where we winter, and CAR-T specialist) seem surprised she hasn't rebounded more they have not been all that worried about the levels as long as she's on a prophylactic regimens of anti-viral, anti-fungal, and anti-biotic meds and haven't been inclined to want to introduce a growth factor at this stage as it may not be sustainable and as we would understand might encourage other than neutrophil growth and expansion, i.e., don't want to risk encouraging anything bad benefiting from a growth factor. Position has been to allow her natural system do it's thing to bring these numbers back into line. She has no prior history of autoimmune issues but did have 6 rounds of R-CHOP, had a clean PET/CT, clean bone marrow biopsy, 18 fractions of consolidative radiation of a remaining small mesentric mass, then on 3/1/23 roughly three months post prior treatments showed DLBCL activity in 2 new areas, another bone marrow biopsy showing no involvement, 3 rounds of polivy/rituximab as a bridge which resolved all signs of disease, a clean PET/CT before the lymphodepletion and 6/26/23 CAR-T so her immune system has taken a beating but not necessarily worse that probably many experience. All her other blood count levels have responded well and basic Rheumatoid Factor and IgG parameters haven't suggested any apparent issues although maybe more in depth testing might be on the horizon.

Welcome @gregolson, I'm sorry to hear that there are no clear answers to the cause or solution for your wife's evolving joint pain. You obviously are doing your homework in searching for answers. I'm tagging fellow CAR-T recipients like @grandpabob @shorheal @wycowgirl307 @annberkowitz and others who have also experience joint and muscle pain.

Has your wife ever been given growth hormone factors (granulocyte colony-stimulating factor) to treat the neutropenia? Did she have an autoimmune condition before being diagnosed with lymphoma?

My wife had CAR-T in June for r/r DLBCL after having had R-CHOP (6 rounds), consolidative radiation (18 fractions), and bridging immunotherapy (3 rounds). Went into CAR-T with a clear PET/CT and low tumor burden. Tolerated the CAR-T as well as can be expected with only margin grade 1 CRS and no neurotoxicity although was still a rough go. Was given Anakinra (Kineret) during her 11 day hospital stay to help ward off CRS and ICANS effects and never needed Tocilizumab. And is now in remission based on her +100 day PET/CT. However, she continues to be neutropenic with neutrophils bouncing around between 600 and 1000 and WBC around 1.6 give or take. Biggest things right now is joint/muscle aches and pain. The PET/CT showed some non-cancerous activity in her right hip area which a subsequent MRI determined to be a muscle 'tear' however she has no recollection of injury and at the time wasn't feeling any pain there but did have pain in the other hip and shoulders which didn't light up in the PET/CT. Orthopedist recommended muscle building and increased protein intake to support muscle rebuilding for the hip. Since then, aches and pains have evolved with left shoulder presenting as the worse. So back to the Orthopedist again and an x-ray shows no joint issues but manipulation leads to suspicion of a rotator cuff issue. Again, no history of injury but she has been an active swimmer most of her life typically swimming 1 to 1 1/2 miles a few times a week. Recommendation was for an MRI but still being immunocompromised prevents any surgical repair so orthopedist dismissed doing an MRI at this time and instead provided some PT exercises to do and recommended a cortisone shot as an interim therapy. Although her CAR-T team are agreeable with her having the shot, we're on the fence for the time being waiting to see how the PT exercises do as some relief seems emergent. The 3 Oncologists she sees throughout the year between our summer and vacation homes and her CAR-T team, are all downplaying the role CAR-T might have in the onset of the joint/muscle pain but another CAR-T support forum on FB and the account of another CAR-T recipient we personally know along with the comments of others here all indicate that this is actually more common than is apparently being talked about by medical professionals. Some good tips have been provided in this thread but we're interested in knowing more about possible links between say neutropenia, auto immune issues, and inflammation triggers that might be in play with the goal of figuring out how to break what seems might be a vicious cycle. In many ways, almost seems like a delayed CRS type of inflammatory response going on and if the CAR-T cells are still active, they may be a contributory part of the problem. And it is interesting that Anakinra is an interleukin-1 receptor antagonist (IL-1Ra) labeled for use in rheumatoid arthritis cases in reducing inflammation and is now being used off label prophylactically against CRS and ICANS while in the hospital. With that, maybe there is a role for Anakinra to be used beyond the acute CRS and ICANS risk period.

Hello Amber, I had Car T in 2018, I have had quite a bit of leg cramping as well even today. I found that doing yoga poses (stretching) has helped a lot, especially those that stretch out the lower body. When I get a bit lazy doing them, the cramps start up again. I agree with you that moving helps a lot.
I have not really found any correlation to my diet, however it makes sense that some foods could affect cramping.

Hi Lori,
What happened requiring CAR T– relapse Non-Hodgkins high grade aggressive DLBCL. Was lucky the FDA approved for folks that had one line of treatment last year. My issues did start until sometime in April, 4 months after treatment. I'm going to try and elevate my legs at night see if that helps. I've always been an active person so I don't think that is it since they started before I began Pilates. Actually I think moving helps.

I'm on the 3 month scan/pet and bloodwork schedule until the end if the year. Last one was at the end of March and my electrolytes and everything else was all good.