- January 19, 2023 at 8:54 pm
I’ve noticed that there is not a ton of information on these boards from folks who have been treated with TIL. For those who may want to know what the experience is like, I’m going to share mine.
I am participating in the following trial at Memorial Sloan Kettering in NYC: Pilot Trial of Autologous Tumor Infiltrating Lymphocytes (LN-144) for Patients With Asymptomatic Melanoma Brain Metastases (NCT05640193). Although the trial is limited to those with asymptomatic brain metastases, the treatment is almost identical to the Lifileucel TIL therapy from Iovance that has been approved for expanded access by the FDA and which has previously excluded those with active CNS involvement.
I was diagnosed Stage 3a in December 2019. I got adjuvant nivo for a year, and remained clear until January 2021, when I progressed in my lung and groin. I did 4 rounds of pembro/low-dose ipi and did not respond. A month later I was thrown off the expanded access TIL trial because of brain mets, which I quickly treated with SRS. After the radiation, I noticed immune side effects (vitiligo, arthritis), and the ground lymph node shrinked. A scan a month later showed almost complete resolution of the existing tumors.
Unfortunately, my three month scans showed one new brain met and several other new subcutaneous lesions. My oncologist at Hopkins (Evan Lipson) immediately referred me to MSK, where this trial was pending approval. It is hard to consider myself “lucky”, but I definitely feel fortunate to have gotten into this when I did, and to have my fact pattern (one, small low-risk untreated brain met). Based on recent data, the docs have quoted a 30% response rate, with a decent chance to “hit a homerun”.
My experience so far
I’m currently sitting in my hospital bed, having just been checked into MSK. I had tumors harvested from subcutaneous lesions in my thighs on December 13th from which Iovance is harvesting and growing my TIL. My initial Baseline testing was November 28th, and my second Baseline testing was January 8th. My wife has relocated from DC and is staying nearby, as I’m required to have a caregiver close at all times.
Tomorrow I’ll get my first dose of the preparatory chemo, which I’ll receive for 7 days total. On day 8 I’ll get the TIL cells. On days 9-11 I’ll receive up to 6 doses of IL-2. I’m required to remain in the hospital for a minimum of three weeks, after which I’ll be moved to MSK apartments a few blocks away where I’ll stay for another 16 days or so. I’m very fortunate to have family to help with my two kids and good health insurance.
I’ll continue to post about my experience every now and then, but also will check in to see if anyone has questions.
Jeff, I hope thinks go smoothly and you get lot’s of T-cells ready for action!!! This following article was published by Iovance at the ESMO conference in the fall of 2022 and published in early December of 2022 on the topic of IL-2 doses and responses based on how much patients could handle and I thought it might be worth a read for you and maybe a discussion with your medical team on the data. https://www.onclive.com/view/lifileucel-induces-response-in-metastatic-melanoma-independent-of-number-of-il-2-doses-received
- January 20, 2023 at 5:02 pm
Jeff, I took this data off the Iovance company home page of the stats with IL-2 numbers and responses. https://www.iovance.com/uploads/Hassel_ESMO-IO_IL-2-analysis-presentation_FINAL-2444-publication.pdf
- January 20, 2023 at 5:19 pm
Jeff, good luck and thanks very much for posting
- January 21, 2023 at 7:28 pm
Your clear explanation will benefit many of us
Thank you, I really hope it works well
PS I have met Evan Lipson a couple of times, he was my second opinion doctor, and both times he was great. His advice the second time round caused my doctors to rethink – we finally gave the TVEC option a chance (not easy to find someone to administer though) and it helped me respond. Am very grateful to him.
Hey all, thanks for your encouragement!
- January 23, 2023 at 9:34 pm
Well things got off too a rocky start. The first dose of chemo (cyclophosphamide) took a toll. That plus not stress dosing my hydrocortisone (adrenal-insufficient) led to the brain met bleeding. My wife was my champion while I was in the throes of headaches, nausea, lethargy and utter brain fog on Friday and into Saturday morning. I am to be tapered on dexamethasone through wednesday and then a stress dose of twice my daily replacement dose of hydro until i’m out of the danger zone.
I’m still recovering from the brain fog and am searching for words. But each day brings improvement. The headache, nausea, and nausea are long gone thanks to some dex and sodium.
I haven’t missed dose of chemo, am still scheduled to get the TIL Friday after consultation with the trial onc, neurosurgery, neurology, endocrinology….the list is too long. I’ve received excellent care, but nothing replaces a good advocate.
Celeste – I’ve been warned about IL-2, but have been told that some react strongly to it and some brush it off. There is no rhyme or reason. Thanks for all you do.
- January 23, 2023 at 9:49 pm
Ed – Yes Dr. Betof told me about this. That is why she is willing to skip a dose or pull the plug on IL-2 if I have a strong reaction. Thanks for pulling the data to support that assertion!
Mark – Yes Dr. Lipson has been my hero (him and is NP Megan). I’m also from DC and visit him at Sibley on Thursdays!
Hi Jeff – sounds terrible but glad that it seems you are recovering. No idea it would be as tough as this. I just logged in by chance and saw you had posted.
- January 23, 2023 at 9:58 pm
I live in DC near the Cathedral – I was treated at Georgetown by Geoff Gibney, he recommended Evan Lipson for second opinions when things were not working and we needed new plans, he recommended adding TVEC to the pembro, and my hero is Dr Rapisuwon at Washington Hospital Centre who made this treatment possible (others didnt want to bother to set it up) (and Dr Boisvert who injected me every two weeks). Dr Lipson always explained clearly and with respect. I dont think he knows his ideas might have saved my life.
Your path sounds tough but I hope it works.
Happy to meet in DC when you get back!
Best wishes Mark
I think it is about past time for an update –
- February 7, 2023 at 10:22 am
Last detailed update I gave was before the TIL infusion, so we’ll start from there.
Recovery from Hemorrhage and Chemo Leading Up to TIL
The last I posted was during my recovery from the hemorrhage, which coincided with the first dose of chemo. I recovered completely over the subsequent days, which primarily included wordfinding difficulties. The remaining chemo doses went by uneventfully, although I noticed some additional fatigue and appetite loss. My initial post states that I’d receive low dose chemo, but I’d since find out that I was receiving relatively high doses. I did start losing my hair, and ended up shaving it bald on day 2 of IL-2. I received cyclophosphamide for the first 2 days and then fludarabine for five days.
Day 0 TIL
Uneventful day. A tech “defrosts” my four bags of milky yellow TIL cells that are infused over an hour. No side effects detected, except for the smell. I smell kinda like organic matter? Or garlic? My wife will tell you that it followed me around like pig-pen for the rest of the day.
I’ll detail the process for the IL-2 and then the side effects, some of which are just the IL-2, but some may be the TILs interaction with the IL-2.
The protocol is to receive up to 6 doses over three days. So they scheduled the doses for around 9 am and 9 pm. The bags are infused over 15 minutes, but pack a punch. I did 2 the first day, and then the morning dose on days 2 and day 4. Each dose brought chills within 2 hours. They’d layer me up with warm blankets. The first day I didn’t have more than a minor fever, but I felt awful. The second night my blood pressure crashed, which triggered a septic warning. I went in for CTs, and ultrasounds, and didn’t get any sleep. I continued to feel awful. The next day/night I battled fevers and high blood pressure, and didn’t get any sleep. I was told the IL-2 would leave my system quickly, but I continued to have high inflammatory markers, and continued to feel bad for several days after.
Here are a list of the side effects brought on by the IL-2, or the TILs inflammatory response, in addition to the above:
Dermatology – (1) Rash on hands and feet, and overall body redness. This has almost completely resolved. (2) My moles have become inflamed, peeled off, or otherwise been infiltrated with TIL. This is uncanny experience, as I have lots of moles. Some are just disappearing.
Liver – My AST/ALT enzymes were through the roof since a few days after the IL-2. They are rapidly normalizing. I’m taking protectant meds daily.
Vision/Hearing – I noticed a decrease in my vision and hearing post IL-2. I’ve seen the optometrist and ENT who think that these are inflammatory responses that will resolve completely or some degree on their own. I’m still impaired, and it continues to bother me.
Headaches/Neuro – I’ve had daily headaches (but not today). Neuro thinks that it is unrelated to TIL/IL-2 at this point, and may just be a blend of brain met pressure and my own physiology.
Appetite – I didn’t have an appetite for several days post IL-2. I’ve just recovered my appetite over the past few days. Savory things taste very salty to me.
Malaise – I felt like crap for at least five days after IL-2
My immune system has recovered sufficiently over the past few days to be discharged, hopefully tomorrow. Key things they look for are Neutrophil values, white blood cells, and platelets, all which have normalized.
I had an MRI last night to investigate my headaches, which revealed further blood and edema in my brain met. This may be a promising sign, per the Neuro, and I have no clinical deficits. However it was scary to read, as it is now 3+ cm, with the intralesional hemorrhage. We are waiting for an opinion from neurosurgery, the trial onc, radiation onc etc.
Let me know it you have any questions about the details.
I’ve been warned several times, however, that everyone responds differently to the IL-2. Some people have a better response than me, and some people end up in the ICU. I think that you’ll need to prepare yourself for some curveballs.
Just to provide an update on my experience with TIL trial….
- February 15, 2023 at 9:48 am
Release from Hospital
I was released from the hospital last Wednesday, which was about 2 days after my blood cell counts normalized (WBCs, platelets and Neutrophils. Hemoglobin and RBC were still a little low) and 3 days after I stopped having headaches. I was in the hospital for 20 days.
I’ve continued to feel more normal over time, particularly with energy and appetite. My hearing and vision have continued to bother me, although I’ve been functional as a NYC transplant. It is more of a nuisance than anything, and they may be improving slowly over time.
I also got my Hickman Catheter removed yesterday. Yay!
I had an appointment with Dr. Imber, a MSK radiation oncologist yesterday. We discussed the results of a multidisciplinary conference that they had in the morning about my case (i.e. including medical oncology and neurosurgery). He told me that, since I continue to have zero neurological symptoms, that they will redo a brain MRI in a month (with perfusion, to analyze blood flow), but also do a Brain PET (which I didn’t know they could do, but he said they can tamp down the normal Brain SUV uptake, and get a sense for how active the lesion is). He said that this will allow the hemorrhage to calm down and will give all parties a sense of what we are actually dealing with (TIL mediated swelling, and a treatment success story? or an active melanoma that has resisted treatment and still needs radiation or surgery). Part of the reason they are resisting treating sooner is with radiation or surgery they will need to give steroids, which will tamp down any of the TIL that are doing good work.
Additional Details About My Experience and That May be Unique
I didn’t mention this in previous posts, but my negative reaction to IL-2 (including the hearing and vision loss) was partially attributed by the Dr.’s to the lack of NSAIDs that would help with IL-2 symptoms. Because of the bleeding brain met, I did not receive the NSAID (sorry I forget the name) that is normal for a TIL trial because of the blood thinning factor. This drug is standard in TIL trials and helps patients deal with IL-2. Just wanted to outline this, in case my situation seemed particularly dire, because I was not afforded this relief that is otherwise available.
Also, I received multiple MRI’s and CT scans in the hospital, and will get the next scan in a month or so. This is primarily off the schedule of the trial, and do to the irregular brain met. The normal schedule for the trial (and other TIL trials) is to rescan at 6 weeks post TIL infusion in order to assess efficacy.
Thanks for sharing your story and details as you have navigated this incredibly challenging process. Though MPIP doesn’t have the traffic it once did, I know your documentation is helping many now and in the future. Hang in there. You are rock’n this out!!!! Fingers crossed that all coming scans demonstrate the best possible outcomes!!!
- February 16, 2023 at 9:46 am
I agree with Bubbles / Celeste – thanks very much for posting. And also for this update including NSAIDs as your treatment sounded pretty bad, so it’s good to know that normally it might be less onerous than what you had to go through – and kept writing to us.
- February 18, 2023 at 5:57 pm
I wish MPIP was more active, but like Celeste I know many will read your description and benefit from it immensely. I may have to get in touch with you too if mine recurs, since I know you are in the DC area. not sure i would have been able to have been treated in New York or received the help you did to make it possible
I hope you are recovering and wish too for good scans
Take care Mark
RIch OParticipantJeff, my wife is also at Hopkins with Evan Lipson and Megan Schollenberger. I came here this morning looking for some TILs experiences which I remembered seeing when she was diagnosed last summer. My wife has progressed on standard of care and 3 weeks ago we went to MSK and UPMC to discuss trials. The consensus was the Iovance TILs were preferred but she doesn’t currently qualify and regardless they are on some kind of a short pause accepting new patients into the cutaneous trials. MSK thought she had a little time to wait, Hopkins thought she didn’t have the time. Over the past week it has become clear that she doesn’t. The docs at Hopkins, UPMC and MSK huddled up yesterday after another scan and an experiment pausing braf/mek. Their recommendation is to immediately pursue the Immatics ATC/IMA203/TILs trial at UPMC that uses leukapheresis instead of resection to harvest the tils. UPMC is calling this morning to discuss the remaining screening. She is still not a lock to qualify. Her remaining tumor might be too large, she had multiple severe irae’s from ipi/nivo and the required 14 day washout from braftovi/mektovi might not be achievable. Your description of the process is very helpful. Apart from the harvesting the process is almost the same. My wife understands it in general but I want her to truly understand what this process will likely entail.
- March 1, 2023 at 7:50 am
We had a call with Megan last week where she mentioned the TILs experiences/outcomes for her patients and at the end said “and one patient who is just finishing up the treatment so it’s to soon to tell”. I’ll bet that is you. Good luck.
Ed Williams, this is Rich O’C from the stage 4 FB group. Which I found last fall from one of your posts in this forum.
Rich – good luck to you and your wife while navigating all of this. I know the amount of uncertainty leading up to a trial acceptance can be very stressful.
- March 1, 2023 at 11:40 am
It is exciting that she is being considered for this TIL trial at UPMC. I visited Dr. Davar there last spring to discuss trials at the time, and had a really good experience with them. They were not offering TIL at the time, but it seems that a lot has opened up since then.
Let me know if you have any follow-up questions about my TIL experience.
- March 20, 2023 at 11:39 am
Last week I had my 6 week follow-up scans and appointments at MSK, and I have good news! There was about 30% shrinkage of the tumors and resolution of the edema in my two brain mets, and 50% shrinkage in my paratracheal lymph node that had been suspicious. On the brain PET there was zero uptake/avidity in the area where I have my tumors – they were completely cold, while the areas around them had normal brain activity. The onc said this was the best result we could hope for, but that more time is needed to assess the results of the TIL treatment.
We are going to hold off on doing anything and reassess at the next 6 weeks scans.
I’ve had a lot of whiplash over the past year, especially after responding to the Ipi/Nivo combo, but then progressing again a few months later. It is hard for my family and I to “celebrate” to much given this, but am really encouraged at this early juncture.
As far as continued side effects from the TIL process, I’m still fatigued by the afternoon, and am completely wiped by bed time. I also still have some vision problems, but they have improved a decent amount since being discharged. My hearing has returned as well, probably 100%. My hair has not yet returned – some facial hair is back, but is completely white. I am still taking the antiviral and bactrim as my lymphocyte subsets are still abnormal, but trending in the right direction. I’ve was also able to stop taking the keppra, which I had been taking since my hemorrhage at the beginning of the chemo.
I’ll post again in 6 weeks, unless something comes up, or if anyone has questions about the process. Thank you all for your support!
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