TIL treatment

Posted By
melmar
8/17/2013 2:19am
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Replies: 36

Thanks to all for responses to my early post, I really appreciate the help. I am wondering if any of you have done TIL and what success or side effects you have had. Thanks in advance for taking the time to respond.

Phil S - (8/17/2013 - 11:58am)

My husband, Phil did TIL at MDAnderson in May 2012 and has been stable ever since. I have said before on this Board, we would do TIL again in a heartbeat! Phil has really enjoyed over one year treatment free and living life. He experienced side effects during chemo depletion, like stomach upset, which were helped with medication. He did two rounds of high dose IL2 with typical side effects, weight gain, blood pressure issues, that all resolved once he completed treatment. The TIL treatment was easier than biochemo. Where are you doing TIL, the protocol at MDAnderson requires two rounds of IL2 while NIH only does one round. All the best, this treatment has worked for husband so far!! Valerie (Phil's wife)

Maureen038 - (8/17/2013 - 3:17pm)

My husband just completed the TIL treatment a week ago at NIH. The doctors and nurses were truly amazing!! Other than fatigue and stomach aches from the antibiotics he is still taking, he is feeling well. He goes back for scans the first week of September. He received 126 billion TIL cells in a 30 minute infusion. He also completed 5 doses of IL2 which are given every 8 hours until they get an immune response. They are extremely cautious in between each dose and he was seen by many doctors during the treatment. We would highly recommend NIH. If you have any questions,feel free to email me at maureen038@aol.com

Maureen038 - (8/17/2013 - 3:38pm)

Also, if you look a tshultz profile and Bob Heffernan profile, they both completed the TIL treatment at NIH. Bob did the protocol three years ago and he is doing amazing. Troy completed the treatment a year ago and he is a complete responder and we were lucky enough to meet him when Bill was there. Bob and Troy were very reassuring and a great source for advice.

BrianP - (8/17/2013 - 6:04pm)

There used to be a really great educational video on MIF about TIL but I just looked and I can't find it now.  I'm in a Nivo/IPI sequential trial right now but TIL is definitely on a short list of options for me if my current trial doesn't work out.  From what I remember from the video and other comments, I think the initial treatment can be tough but once the TIL infusion starts it's not too bad.  Some numbers I remember hearing at one time or another is that about 80% of patients are successful with harvesting their TIL.  Of those 80% about 40% have "durable" responses (do your own due diligence on the stats but that's what I remember).  One of the requirements that I remember about the NIH trial is that you have to have resectable melanoma that they can harvest the TIL cells from and the surgery has to be performed there.  One nice thing about those that do have responses is that it is pretty quick acting and the ones that have a complete response and go past 2 years appear to be "cured".  Cured and melanoma are two words you don't often hear in the same sentence. 

The link below is to a quick 3 minute presentation by Dr. Rosenburg at NIH.

http://www.youtube.com/watch?v=fY5ptp9I4jU 

Good luck to you!

Brian

Anonymous - (8/18/2013 - 8:25am)

I lost my young best friend who was told TIL would cure her.  I can't find any statistics or a clinical trial that proves this has such high responses as Brian said.  She only had local type disease and was in really good health otherwise.  She never came back from the drugs they used.  They don't talk about this treatment at ASCO or other conferences and there are questions about the huge cost.  Be very careful before you choose this, you don't hear about the those who didn't respond because they are no longer with us.

POW - (8/18/2013 - 10:10am)

Steve Rosenberg at the NIH pioneered the use of "tumor infiltrating lymphocytes" (TIL) to treat various types of cancer, including melanoma, 15 years ago. From that time to this, the technique has been attempted at various institutions around the world but has never gained wide acceptance. From what I can tell from the medical literature, the technique is appropriate for a limited subset of patients, it is technically very difficult and and medically expensive, and the side effects can be severe. According to a report out of Europe last year ( http://www.translational-medicine.com/content/10/1/169 ) of 11 patients accepted to their TIL trial, only 6 were actually treated. Of those 6, only 2 experienced a remission lasting longer than 5 months. Can it work? Yes. Will many melanoma patients be likely to benefit significantly? I don't think so. 

Maureen038 - (8/18/2013 - 11:26am)

I have no problem with everyone making their own decision for treatment. I do mind people not using their name to post something that may or may not be true about someone dying. I know that at NIH we were not promised a cure ever. Treatment for metastic melanoma is an agonizing choice and we relied on scientific journals to make our decision. One of the problems with MPIP is there is not a fact checker. People can write whatever they want. I have a serious issue with that and I have written Tim about this difficulty. By the way, adoptive cell transfer was discussed at ASCO 2013. Look at the abstracts. Also, google Dr. Steven Rosenberg and you will find he has been awarded many top awards for cancer research and was the most cited researcher in cancer for 17 years. He also has journal articles on all of his clinical studies and results for ACT. Dr Weber at Moffitt and Dr. Hwu at MD Anderson are using ACT now too and there are two companies that are trying to make it possible for ACT to be a standardized treatment for phase 3 studies.
My husband and I both feel that ACT should not be the last option when your body is weakened and melanoma may have spread to many places, but should be earlier in the treatment options. My husband is doing well even though it was a tough treatment because he was in good shape before he started the treatment. We received outstanding care at NIH!!

Maureen038 - (8/18/2013 - 11:28am)

I have no problem with everyone making their own decision for treatment. I do mind people not using their name to post something that may or may not be true about someone dying. I know that at NIH we were not promised a cure ever. Treatment for metastic melanoma is an agonizing choice and we relied on scientific journals to make our decision. One of the problems with MPIP is there is not a fact checker. People can write whatever they want. I have a serious issue with that and I have written Tim about this difficulty. By the way, adoptive cell transfer was discussed at ASCO 2013. Look at the abstracts. Also, google Dr. Steven Rosenberg and you will find he has been awarded many top awards for cancer research and was the most cited researcher in cancer for 17 years. He also has journal articles on all of his clinical studies and results for ACT. Dr Weber at Moffitt and Dr. Hwu at MD Anderson are using ACT now too and there are two companies that are trying to make it possible for ACT to be a standardized treatment for phase 3 studies.
My husband and I both feel that ACT should not be the last option when your body is weakened and melanoma may have spread to many places, but should be earlier in the treatment options. My husband is doing well even though it was a tough treatment because he was in good shape before he started the treatment. We received outstanding care at NIH!!

Cooper - (8/18/2013 - 11:54am)

No one at MDA or Moffitt have been able to get the same results as Rosenberg.  Most docs agree it is because of the NIH way of gathering statistics and only allowing the young and fit to enter the trials.  I read that it costs $500K per patient at NIH for til so you should be getting good treatment as it is on the taxpayers to pay for your care.  Many extra scans etc are done because there is no insurance company on the sideline, so they can run up huge bills.  Cost aside, the phase III trial results against one of the new treatments hasn't been published.  That should be the facts in your arsenal Maureen.  And maybe someone wants to be anonymous for a personal reason and that shouldn't bother you.  POW backed up her facts with a study.  Where are the ASCO abstracts?

benp - (8/18/2013 - 8:50pm)

Obviously, this is a very effective treatment for a large number of patients. Just because it may not be suitable for everyone does not mean it should not be available to those that are, especially given the results out of NIH, MD Anderson, NIK (Holland), Sheba (Israel) and elsewhere.

 

It does not cost $500k. I know, because I paid for it in full. It was around $100k all inclusive.

 

It is true that this is a laborious treatment, and there a few financial incentives as it is not a drug (as is Ipi, Lambro, Zelbo etc.) and not patentable. Perhaps this is why it has not been able to go through trials as quickly as the drugs listed above.

 

Ben.

JerryfromFauq - (8/18/2013 - 11:45pm)

NIH does not present a BILL.  That may be their cost, I don't know that.

Yes, cherry picking does allow one to get better results.  I don't know how  much MDA and Moffit restrict who they let in.  I do know that a few years ago MDA turned down a lady I know, who is still fighting melanoma may well be to weak to try TIL now.  One thing is that they know better who to try things on if they can determine the criteria as to who will best benefit from it.  I often think places are too restrictive in trials, but do understand some of why from the scientific side of things.  By cherry pickiing they caan raise the odds on helping certain people from 0-1 perscent to 50% at times.  in the long run it saves patients and insurance money and gets quicker result for the cherry picked ones.

I'm me, not a statistic. Praying to not be one for years yet.

Peabody_58 - (8/18/2013 - 1:03pm)

I have read the posts on adoptive cel therapy with interest as I am one of the patients of Rosenberg in the NIH study.  I have a strong scientific background and significant experience with immunotherapy in the clinic (not for melanoma).  From my perspective, as a melanoma patient, I considered my options for treatment as follows:  (1) surgery when possible; (2) PD-1 or PD-1/Ipi  (3) Radiation + PD-1 or Ipi  (4)  Ipi alone (standard of care)  (5) vaccine immunotherapy and (5) adoptive cell therapy, what I considered to be my best option.   

The cost of the Adoptive Cell Therapy is high - over $100,000 per patient - but since it is a clinical study, the cost is borne by the research institution.  It is a equitable trade in my mind because for a period of time you turn your care over to the research institution which takes a large sampling of tissues to help them understand their treatment approach.  Without volunteers, there would be no progress on any research, so it is a fair quid pro quo.  The cost sets the barrier for the pharma companies because they do not see a path to profitablity with these therapies...that is price we pay in a for-profit health care system.

The therapy itself, and immunotherapy in general, provides the melanoma patient with the best chance for a CURE.  For me, I was seeking a CURE first and then remission second.  The key to a cure is to get at the progenitor cells that are the source of the metatastic tumor sites.  There is no drug currently available that will achieve this result.  There are a number of research papers that have been published recently including at ASCO on the topic....here are a couple:

from the 2013 ASCO meeting:

http://meetinglibrary.asco.org/content/111332-132

and from Rosenberg's lab:

http://www.researchgate.net/publication/230762206_The_Stoichiometric_Production_of_IL-2_and_IFN-_mRNA_Defines_Memory_T_Cells_That_Can_Self-Renew_After_Adoptive_Transfer_in_Humans/file/79e4150476a7ebf345.pdf

A number of the references in the Roseberg paper should be helpful in guiding you to own decision as to whether to participate in this study.  For me, it was obvious.

Do or do not, there is no try

Cooper - (8/18/2013 - 2:19pm)

If you  have a science background then you should know that no treatment is proven until it goes through phase III trials comparing it with another agent for overall survival.  Showing papers from one source (Rosenberg) is not a fair way to look at things in science, you must compare it with other authors who aren't trained by him or are pressing for TIL.    If it truly provides a cure than where is the evidence?  Haven't seen it, only a few years survival at most.  So I hate to see anyone have false hope that is the worst!  By the way it is our money, the public citizen, who pays for Rosenberg's trials and your therapy.  Not the "research institute" and I'd like to see NCI look at newer stuff than IL2 with my money.

BrianP - (8/18/2013 - 4:24pm)

Cooper,

I tend to think about it a little different concerning the use of your's and my taxes to fund these studies.  As has been stated in an earlier post, this is a pretty expensive treatment and the ability to treat patients and make money in the future with this treatment is tough to argue.  So whose going this type of research?  The pharmaceutical companies certainly aren't.  I've watched a couple webinars on the procedure and I think it is definitely a worthwhile pursuit.  There was a webinar on MIF that Dr. Rosenberg did within the last year.  He reported some very impressive results.  Yes I have heard the same point you made that other places are not reporting the same success but I guess I chose to give the guy a little bit of trust.  After all he's devoted probably around 30 years of his life in pursuit of a cure for melanoma.  It's a little peculiar that Catherine Poole (the founder of MIF) has taken the webinar down.  I know she shares some of the same opinions you do concerning this particular treatment at NCI.  The link below is a webinar that Dr. Weber from Moffitt gave on Adoptive Cell Therapy a couple years ago.  Unfortunately it doesn't give as many statistical results as the webinar that was removed but there is one study result given around the 17 minute mark.  One of the reasons I think the TIL research is so worthwhile is because of the potential in combination treatment with other drugs such as IPI and anti PD-1.  Dr. Weber mentions that toward the end of his presentation.  BTW, in full disclosure, Dr. Weber worked for Dr. Rosenberg for about 15 years prior to going to Moffitt.

http://melanomainternational.org/webinar/2012/02/adoptive-cell-therapy-for-cancer/?done=1 

Brian

JerryfromFauq - (8/19/2013 - 12:05am)

Where's the LIKE button?

I'm me, not a statistic. Praying to not be one for years yet.

Peabody_58 - (8/18/2013 - 4:42pm)

http://clincancerres.aacrjournals.org/content/17/13/4550.full.html#ref-list-1

The above report is the most recent summary from Rosenberg's lab.  There are other facilities now offering TIL therapy and there are a number of recent publications and comments on how to improve the therapy (See Herlyn's recent letter).  No therapy is going to be perfect and no therapy carries any guarantees.  One of the most frustrating things about human therapy is that every patient is different and every cancer is unique.  One can only make the best assessment of the therapies available and make the choice that seems to give you the best chance for success.  I do not feel it is necessary to reference the hundreds of immunotherapy papers in my personal library; I only cited a couple of papers that I thought were germain to this particular discussion.  There are some very exciting developments in non-melanoma immunotherapy that suggest personalized medicine will yeild significant results in the future.

Regarding the Phase II aspect of the study, this is clearly due to the fact that the protocol is not optimized.  The primary objective for Phase II is to determine optimal dosing conditions to achieve a clinically significant response.  With a therapy as complicated as this one, it may take years before they have something that they believe is going to be ready for Phase III.  That is part of the risk factors that one has to consider before entering a trial.  My study is intended to determine if radiation therapy improves the results.  In my view, they would be wise to consider incorporating PD-1 before or after delivery of the TIL cells.  I am sure that will be a future study cohort.

One other factor for everyone to consider irrespective of the in which study you may choose to enroll is the fact that any study may disqualify you from participating in another study that you want.  For me, if I went into the Ipi/PD-1 study, a common side effect may have eliminated me from consideration in the Adaptive Cell Therapy study.  It was a big consideration.   If the TIL cells don't deliver for me, I still have options.  That was a factor for me.

Finally, regarding the support by NIH funding, I suggest you read the commentary by George Will in today's Washington Post.http://www.washingtonpost.com/opinions/george-will-the-sequester--a-public-health-hazard/2013/08/16/4bb96982-05ca-11e3-9259-e2aafe5a5f84_story.html  There is no greater asset to our country than the health of our citizens and curing cancer, heart disease, diabetes and the many other diseases under study at the NIH are crucial to our future.  Is it your view that you want to turn over all drug development to the Pharamaceutical Industry?  If you do, you can forget seeing the development of anything that does not meet the criteria of the Pharma marketing team.  As a case study, look at Ipi and anti-PD-1 at BMS.  BMS could have had PD-1 on the market long ago but held back because of their investment in Yervoy.  It was not until a competing product from Merck showed up that things finally got moving at BMS.   As it happens, IL-2 is still a viable option that actually works for some all by itself.  Maybe there are ways to get better than a 20% success rate...that would be money well spent.

Do or do not, there is no try

BrianP - (8/18/2013 - 5:06pm)

Thanks for posting this link Peabody.  Those statistical results are the numbers I was having a difficult time recalling from the webinar.  The one that stood out to me was the 20 of 93 patients who obtained a durable.  Even more impressive was of those 20 who did obtain a durable response only 1 had a recurrance.  Many of those are now well past 5 years.  I also remember that as the trials progressed and they tweeked the process their results continued to improve.  This brought me to the conclusion that the next 93 patients would probably have even better results than the first 93 patients.

One comment you made that I will have to look into is the point about other treatments disqualifying you for TIL.  I seem to remember one of the advantages to TIL was that since it was a slightly different approach that not many other treatments disqualified you from the  TIL trial.  I need to go back and look at that.

Brian

Peabody_58 - (8/18/2013 - 5:23pm)

I believe it is some liver function problem that crops up with Ipi that was a potential disqualifier.  The other biggie is brain mets, which fortunately at the time of my screening I did not have.  I can always go back and take the Ipi or the PD-1.  My first clinical study was low dose Ipi, but I got relegated to the control group (IFN).  Then when I went to Sharfman for the PD-1, it was going to be months before I could get into that study, so he sent me to Slingluff (UVA) who had a very weak peptide vaccine.  

Do or do not, there is no try

POW - (8/18/2013 - 2:58pm)

The ASCO 2013 report that you linked to is authored by the same group in Denmark that published the 2012 paper that I linked to. In 2012, they had accepted 11 patients into their study of whom only 6 actually received the treatment. Of those 6 patients, 2 showed a complete response for longer than 5 months. A year later, in 2013, they had accepted (i.e. attempted to treat) a total of 31 patients but actually treated a only 15 of whom 3 showed a complete response (presumably including the 2 complete responders from the prior year's report). Based soley on percentages, 2 out of 6 (33%) is better than 3 out of 15 (20%)-- more patients and more investigator experience do not appear to be improving the outcomes. And if you consider all of the patients who went through all the testing and had their tumor cells harvested for T-cell culture (31 people), only 3 have been in remission for more than a year-- that's 10% of the "attempt to treat" group.

I'm not sure how useful it is for most of the people here for us to parse the exact details of these scientific studies. I just don't want patients or families who are desperate for a cure for their melanoma-- or even a long-lasting remission-- to think that TIL is the be-all and end-all of melanoma treatments just because it comes from the NIH. TIL works very well for a few patients, it works OK in some patients, and it works not at all in some patients. And still nobody can predict who will respond to which treatment. Just like everything else we have available to us.  

Peabody_58 - (8/18/2013 - 5:10pm)

The paper in my second post is a more detailed response of Rosenberg's work summarizing the results of 93 patients.  Statistics are what they are...tools to make an argument.   The data provides clues, not guarantees.

My last word on this topic is to do your research, weigh your options and do what you think is best for you.  I saw every top melanoma specialist in the region before I decided.  I would suggest doing the same and then talking it over with your oncologist.  Every patient needs a team: family, onocologists, melanoma specialists and melanoma researchers.  Use every resource at your disposal to try to beat this disease.   Every day brings us closer to new drugs and therapies.  We must fight on!

Do or do not, there is no try

Phil S - (8/18/2013 - 5:18pm)

My husband was offered TIL by Dr Wen Jen Hwu and Dr Patrick Hwu at MDAnderson in May 2012, after he had done six rounds of biochemo. My husband was hardly considered a stable, strong, or healthy Stage 4 melanoma patient. He had brain mets and had done WBR in the Fall of 2011. At the time of TIL, he had multiple lung mets, abdomen mets, others scattered around, and was clearly having tumor growth. Dr Patrick Hwu runs an excellent program at MDAnderson, and we are so glad they took a chance on treating Phil with TIL. Our care was excellent, they were very quick to treat all side effects. When we were offered TIL, we went to see Dr Hodi at Dana Farber (our original and current doctor) and he said go for it. We have never looked back, it changed the forward progression of Phil's melanoma for now. We know we are probably not out of the woods, but we have always believed that attacking melanoma is a constant and varying fight. If needed, we would love to try Ipi and/or AntiPD1, and possibly if we are lucky other drugs discovered in clinical trails. I am proud that Phil participated in the TIL trial and hope they got good data from him to help others down the road. In the future, they will be able to better predict who will have a response and who won't, but we aren't there yet.
I support and applaud every single person who fights this Beast, and I don't offer any negatives on their choices. Just fight hard, don't look
back, and keep the Faith! Valerie (Phil's wife)

Maureen038 - (8/18/2013 - 6:47pm)

Obviously there is a lot of passion in the different opinions for ACT. I believe that everyone is entitled to their opinion, but my husband and I get upset when we read some of the posts that show part of the results of a trial, but not all of the trials for ACT. We believe strongly that this is his best chance for long term remission.  Dr. Rosenberg and his staff are working diligently and fine tuning each trial. From the following article you can see how far they have come in growing TIL cells. http://www.ncbi.nlm.nih.gov/pubmed/20842052. It is amazing to us to see so many people working so hard for a cure or an objective response. I think its a very complicated protocol and perhaps in a couple of years Moffitt and MD Anderson will have similiar results. Here are the results from Israel that are the same as NIH.http://www.hindawi.com/journals/cdi/2010/260267/   Im sorry if I seemed insensitive to the person that died. This is the most difficult experience in my life  to see someone I love so dearly go through this disease. Just please dont rule out any treatment because of someone else"s experience. Everyone is different.

Brian, IPI can have a side effect that can make you take steriods. if that happens, you can't participate in the ACT. Also, you cant have any more than three brain mets. you can email him directly at SAR@nih.gov   I wish everyone the best!

BrianP - (8/18/2013 - 8:58pm)

Thanks Maureen,

I actually just recently enrolled in a PD-1/IPI sequential clincal trial at UVA.  I was looking very closely at the ACT trial back in May when mets were found in my small intestines during an endoscopy procedure.  I really wanted to give the ACT a try but based on the pictures and the characteristics of the mets they saw during the endoscopy the nurse I spoke with at NCI didn't think they would be successful at harvesting the TIL from my mets.  I was told that it can be difficult sometimes to harvest mets from the intestine area due to contamination from the bacteria.  Based on that information I had the resection at Duke with a surgical oncologist I had a lot of trust in.  Hindsight being 20/20, after the surgery we discovered the mets they saw on the endoscopy were actually the smallest of my mets and there probably would have been more than enough "material" to harvest the TIL cells from.  Oh well, you make the best decisons you can with the information you have at the time.  I hold out hope that I won't need any future treatments after the PD-1/IPI treatment but if I do I will definitely consider ACT again if my circumstances permit.

Brian

Maureen038 - (8/23/2013 - 10:09pm)

Good luck Brian! I think the Ipi/pd1 is an excellent trial and hopefully you won't need ant other treatment.

DonnaK - (8/23/2013 - 3:05pm)

I know this is an older thread but I wanted to respond for anyone else considering TIL therapy.  My husband "qualified" for the trial at NIH and had a lymph node extracted for TIL expansion.  Unfortunately, by the time his TILs were ready, he was disqualified from the actual trial due to numerous brain mets.  We did alot of research and felt confident that this trial was his best chance at long term survival, but I thought I'd put it out there that the waiting time btw extraction and re-implantation can be lengthy (3-6wks).  I know there is no way to predict how rapidly melanoma will spread, but I would caution anyone who waits for extended times btw treatments to qualify for any trial, including this one. In retrospect, I don't know that I would do anything differerently, but I think it's important to understand how much can change in just a few weeks. In my husbands case he had very limited disease in lungs/lymph nodes when he was first diagnosed on Apr 16, and "innumerable brain mets" on May 23. Just another POV...
 

Best of luck with your decision.

Donna

Anonymous - (8/23/2013 - 4:11pm)

And some folks aren't accepted into the trials because they aren't the perfect candidate.  Sometimes the Til cells don't grow.  But the worst part is when they take your immune system away and then try to bring it back.  Just to risky for me.  Bone marrow transplants do the same and they are now found to be not so useful after many years.

Maureen038 - (8/23/2013 - 9:13pm)

Every clinical trial has exclusions and inclusions. At NIH they have a 90 percent chance of growing your TIL cells. They are extremely careful during the whole treatment and especially when you are neutropenic. In my opinion it is the best treatment for long term regression or even more amazing a cure!

Cooper - (8/24/2013 - 7:45am)

Maureen,

 Where is the 90% chance of growing TILs published?  Not sure that is a proven fact but probably something said there.  Time will tell for this treatment but I hate to see false hope being given  for something being a cure being said.  It just isn't for everyone.  The good thing are the new treatments that are working!  IPI/Pd1 is a great trial!

Maureen038 - (8/24/2013 - 7:34pm)

I am not trying to give false hope. I am trying to show it is a viable and highly effective treatment. Just because a treatment shows a high success rate doesnt mean it will work on my husband though or other people. We each take a chance with each trial and hope and pray that this treatment will work. We have not gone for scans yet, but even if it doesnt work we truly believe in the treatment. There are other treatments that work too, but its a personal choice. Melanoma is a scary enough disease without taking to frightening people that there is no chance for it to work. That is not okay either.

Here are some articles

http://www.ncbi.nlm.nih.gov/pubmed/20842052

 

http://www.ncbi.nlm.nih.gov/pubmed/11041020

 

http://www.ncbi.nlm.nih.gov/pubmed/22421946

 

http://www.translational-medicine.com/content/9/1/107

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