Tils LN-144/LN-145

I wish you and your wife my best. Celeste

Long post coming up

My experience of TILs therapy.

TILs = Tumour Infiltrating Lymphocytes

Royal Marsden Hospital (RMH) TILs trial, Protocol C-144-01. Sponsored by Iovance Biotherapeutics Inc.

I was invited to join the TILs trial after previous Ipi/Nivo imunnotherapy had failed and now stage IV. I had been told I couldn’t have anymore Immunotherapy due to toxicity issues and nor would I be offered any more surgery, chemotherapy was all that was on offer, efforts would be made to investigate new therapies in development. Needless to say I wasn’t thrilled at the prospect of Chemo.

The day before starting chemo I was told about the TILs trial and offered the chance to take part in it, as I’m sure you can imagine I bit their hand off. I was the first patient on a very small sample of only three places at this hospital. I later found out that this trial had been entrain for six years. On reflection I feel very fortunate to have engaged with the trial.

A metastatic tumour on my right shoulder/arm was removed by surgery on the 29th October 2019. The tumour mass had appeared on top of a scar site of another previously removed metastatic mass. The tumour mass was couriered to one of the the sponsors European laboratory facilities in Holland. The Lymphocyte cells that had identified and attempted to attack the cancer were harvested from the tumour mass and grown in number over the next four weeks. Prior to Hospital admission I was fitted with a Hickman line in my chest (painless) in readiness for all blood tests and infusions.

On the 3rd December I was admitted to the Royal Marsden Hospital London and placed in a private room in the Wiltshaw Ward that specialises in stem cell transplants and similar transplant therapies.

Week one involved receiving infusions of chemo drugs, Cyclophosphamide for two days and Fludarabine for five days to delete my immune system to near zero making space for the new cells. Deemed Neutropenic, all my room visitors including staff had to thoroughly wash hands and put on plastic aprons. I was forbidden to eat any uncooked foods such as salad or unpeeled fruit. At this stage I found the chemo treatment reasonably undemanding. side effects included some hair loss and loose stools.

24Hrs after the last dose of Fludarabine, the Lymphocytes that had been grown in huge numbers arrived back at the RMH having been held at RMH Sutton since arriving back in the UK.

Being the first patient in the RMH trial there was great interest from Professor Larkin’s research team under Dr Andrew Furness and the Wiltshaw ward nursing team who would administer future treatments. At one time thirteen people were in the room observing but I was comfortable with this.

The Lymphocyte material arrived in the room in a large Cryogenic bin on a trolly. Inside were three cassettes containing the bags or sachets of my Lymphocytes in a milky solution. I was told that the Lymphocytes had been mutiplied to an estimated nine billion cells, contained in three bags. For experience, staff took turns to remove the frozen bags and defrost them in a warm waterbath set to 37 degrees C. The Lymphocyte solution was infused via the Hickman line. Once again this was an interesting but undemanding process for me.

The morning after receiving the infusions of the estimated nine billion Lymphocyte cells I received my first dose of Interleukin 2. This is the part you’ve probably heard of and the part I was slightly anxious about.

I had been taken off all blood pressure medications in anticipation that my blood pressure could fall dramatically but of course I bucked this trend and at times my BP went to 240/xx. some BP meds were re-introduced. I had been warned that I might be transferred to the ICU for closer monitoring but this never became necessary.

The interleukin 2 was infused as I lay on the bed wearing loose hospital pyjamas . After approximately forty minutes I started to feel cold chills on my back and saw goosebumps on my arms, within a few seconds I started to shiver and shake uncontrollably with my teeth chattering and unable to speak coherently .

I hadn’t appreciated that although I was feeling extremely cold, my core temperature was heading up to 40+ C. My breathing became very rapid, almost hyperventilating. This is probably the most distressing aspect of this therapy but breathing can be controlled. Nursing staff were very encouraging and urged me not to resist the rigors that came in strong waves. As soon as the shaking started the nurses administered Petherdine via an IV drip which soon relaxed muscles and made the rigors feel less severe. During this time I was given an oxygen mask with a nebuliser attached to assist in breathing which had become a little wheezy.

Unfortunately the first IL2 infusion took place shortly after breakfast and I suddenly felt nauseous and was sick. On a lighter note my projectile vomit impressed all present… Eventually the shaking and breathing calmed and I returned to normal.

First impression was that the process was not too distressing and I was not too worried about the next IL2 infusion later that day. The next IL2 infusion was better, I wore pyjamas bottoms and a close fitting but stretchy tee shirt/vest, this felt more comfortable when the chills started.

During the day I’d had time to ponder the mornings events and realised that although my breathing felt very rapid and light I hadn’t come anywhere close to blacking out or losing consciousness at any time. The second dose was more relaxed probably thanks to the presence of Nurse Hilary who was making the nursing team laugh and relax, I’m not sure what she was saying but it was infectious, shaking strongly, teeth chattering and wearing an oxygen mask I was laughing too. Breathing was rapid again but I noticed my oxygen saturation on the Obs machine was 96-100%, Ifound this an extremely useful feedback loop which helped my confidence greatly, I was then able to try regulate my breathing rate, breathing in through my nose and out through my mouth, I needed regular sips of water as my mouth became dry. I also noticed that the rigors came in waves almost like being on a roller coaster. I later fed this experience back to staff who were able to call out oxygen levels in the following infusion sessions.

Fortunately I was able to tolerate six out of a maximum of six doses of IL2 but I’m not saying it was easy.

Conclusions. I know we are all different in MelonomaMates many of us have very different responses to the same drugs, it seems I may have have tolerated the treatment easier than some others and I don’t wish to demean their experience in any way.

After the IL2 I came out in a spectacular rash on my head upper torso and legs, interestingly there was some obvious inflammatory activity around the subcutaneous lesions. I am cautiously finding some lumps have receded, though scans planned for January will provide the definitive proof.

My partner sat next to me during the IL2 infusions, bear in mind that loved ones looking on may have a different impression of what you are experiencing and they will feel helpless and distressed that they are unable to help.

After the final IL2 I had a few temperature spikes which settled down after a few days. I developed a ticklish cough, and shortness of breath which was checked out with X Rays. A small blood bourne infection was discovered caused by the Hickman line and IV Antibiotics were administered. There was some lymphedema in my legs adding about four kilos to my weight this is a known side effect of IL2. One week on and the lymphedema is back to normal due to wearing compression stockings and exercise of climbing stairs, walking about etc.

Blood tests showed I that I required three units of blood platelets and two units of red cells. Once my immune system was back to near normal I was discharged from hospital on 22nd December ( nearly three weeks in all ).

I noticed that I had slight breathlessness and muscle weakness in my legs when walking but otherwise felt reasonably normal if a little tired.

I hope this has been of use to anyone about to undergo TILs. Also I’d like to say that thanks to the professionalism and expertise of the doctors and especially the nursing staff who treated me, at all times I felt safe and confident in the delivery of this unusual treatment.

Long post coming up

My experience of TILs therapy.

TILs = Tumour Infiltrating Lymphocytes

Royal Marsden Hospital (RMH) TILs trial, Protocol C-144-01. Sponsored by Iovance Biotherapeutics Inc.

I was invited to join the TILs trial after previous Ipi/Nivo imunnotherapy had failed and now stage IV. I had been told I couldn’t have anymore Immunotherapy due to toxicity issues and nor would I be offered any more surgery, chemotherapy was all that was on offer, efforts would be made to investigate new therapies in development. Needless to say I wasn’t thrilled at the prospect of Chemo.

The day before starting chemo I was told about the TILs trial and offered the chance to take part in it, as I’m sure you can imagine I bit their hand off. I was the first patient on a very small sample of only three places at this hospital. I later found out that this trial had been entrain for six years. On reflection I feel very fortunate to have engaged with the trial.

A metastatic tumour on my right shoulder/arm was removed by surgery on the 29th October 2019. The tumour mass had appeared on top of a scar site of another previously removed metastatic mass. The tumour mass was couriered to one of the the sponsors European laboratory facilities in Holland. The Lymphocyte cells that had identified and attempted to attack the cancer were harvested from the tumour mass and grown in number over the next four weeks. Prior to Hospital admission I was fitted with a Hickman line in my chest (painless) in readiness for all blood tests and infusions.

On the 3rd December I was admitted to the Royal Marsden Hospital London and placed in a private room in the Wiltshaw Ward that specialises in stem cell transplants and similar transplant therapies.

Week one involved receiving infusions of chemo drugs, Cyclophosphamide for two days and Fludarabine for five days to delete my immune system to near zero making space for the new cells. Deemed Neutropenic, all my room visitors including staff had to thoroughly wash hands and put on plastic aprons. I was forbidden to eat any uncooked foods such as salad or unpeeled fruit. At this stage I found the chemo treatment reasonably undemanding. side effects included some hair loss and loose stools.

24Hrs after the last dose of Fludarabine, the Lymphocytes that had been grown in huge numbers arrived back at the RMH having been held at RMH Sutton since arriving back in the UK.

Being the first patient in the RMH trial there was great interest from Professor Larkin’s research team under Dr Andrew Furness and the Wiltshaw ward nursing team who would administer future treatments. At one time thirteen people were in the room observing but I was comfortable with this.

The Lymphocyte material arrived in the room in a large Cryogenic bin on a trolly. Inside were three cassettes containing the bags or sachets of my Lymphocytes in a milky solution. I was told that the Lymphocytes had been mutiplied to an estimated nine billion cells, contained in three bags. For experience, staff took turns to remove the frozen bags and defrost them in a warm waterbath set to 37 degrees C. The Lymphocyte solution was infused via the Hickman line. Once again this was an interesting but undemanding process for me.

The morning after receiving the infusions of the estimated nine billion Lymphocyte cells I received my first dose of Interleukin 2. This is the part you’ve probably heard of and the part I was slightly anxious about.

I had been taken off all blood pressure medications in anticipation that my blood pressure could fall dramatically but of course I bucked this trend and at times my BP went to 240/xx. some BP meds were re-introduced. I had been warned that I might be transferred to the ICU for closer monitoring but this never became necessary.

The interleukin 2 was infused as I lay on the bed wearing loose hospital pyjamas . After approximately forty minutes I started to feel cold chills on my back and saw goosebumps on my arms, within a few seconds I started to shiver and shake uncontrollably with my teeth chattering and unable to speak coherently .

I hadn’t appreciated that although I was feeling extremely cold, my core temperature was heading up to 40+ C. My breathing became very rapid, almost hyperventilating. This is probably the most distressing aspect of this therapy but breathing can be controlled. Nursing staff were very encouraging and urged me not to resist the rigors that came in strong waves. As soon as the shaking started the nurses administered Petherdine via an IV drip which soon relaxed muscles and made the rigors feel less severe. During this time I was given an oxygen mask with a nebuliser attached to assist in breathing which had become a little wheezy.

Unfortunately the first IL2 infusion took place shortly after breakfast and I suddenly felt nauseous and was sick. On a lighter note my projectile vomit impressed all present… Eventually the shaking and breathing calmed and I returned to normal.

First impression was that the process was not too distressing and I was not too worried about the next IL2 infusion later that day. The next IL2 infusion was better, I wore pyjamas bottoms and a close fitting but stretchy tee shirt/vest, this felt more comfortable when the chills started.

During the day I’d had time to ponder the mornings events and realised that although my breathing felt very rapid and light I hadn’t come anywhere close to blacking out or losing consciousness at any time. The second dose was more relaxed probably thanks to the presence of Nurse Hilary who was making the nursing team laugh and relax, I’m not sure what she was saying but it was infectious, shaking strongly, teeth chattering and wearing an oxygen mask I was laughing too. Breathing was rapid again but I noticed my oxygen saturation on the Obs machine was 96-100%, Ifound this an extremely useful feedback loop which helped my confidence greatly, I was then able to try regulate my breathing rate, breathing in through my nose and out through my mouth, I needed regular sips of water as my mouth became dry. I also noticed that the rigors came in waves almost like being on a roller coaster. I later fed this experience back to staff who were able to call out oxygen levels in the following infusion sessions.

Fortunately I was able to tolerate six out of a maximum of six doses of IL2 but I’m not saying it was easy.

Conclusions. I know we are all different in MelonomaMates many of us have very different responses to the same drugs, it seems I may have have tolerated the treatment easier than some others and I don’t wish to demean their experience in any way.

After the IL2 I came out in a spectacular rash on my head upper torso and legs, interestingly there was some obvious inflammatory activity around the subcutaneous lesions. I am cautiously finding some lumps have receded, though scans planned for January will provide the definitive proof.

My partner sat next to me during the IL2 infusions, bear in mind that loved ones looking on may have a different impression of what you are experiencing and they will feel helpless and distressed that they are unable to help.

After the final IL2 I had a few temperature spikes which settled down after a few days. I developed a ticklish cough, and shortness of breath which was checked out with X Rays. A small blood bourne infection was discovered caused by the Hickman line and IV Antibiotics were administered. There was some lymphedema in my legs adding about four kilos to my weight this is a known side effect of IL2. One week on and the lymphedema is back to normal due to wearing compression stockings and exercise of climbing stairs, walking about etc.

Blood tests showed I that I required three units of blood platelets and two units of red cells. Once my immune system was back to near normal I was discharged from hospital on 22nd December ( nearly three weeks in all ).

I noticed that I had slight breathlessness and muscle weakness in my legs when walking but otherwise felt reasonably normal if a little tired.

I hope this has been of use to anyone about to undergo TILs. Also I’d like to say that thanks to the professionalism and expertise of the doctors and especially the nursing staff who treated me, at all times I felt safe and confident in the delivery of this unusual treatment.