CAR-T Therapy Archives - Living with Lymphoma

Having CAR-T Therapy

In my previous post, I talked about what CAR-T therapy is and the process of preparing to have it. In this post, I explain the actual procedure I went through.

Having been extracted and flown over to America, my genetically modified T cells arrived back in the UK three weeks later. It was now time to prepare my immune system to receive them back. This meant yet more chemo! The purpose of this lymphodepleting chemo was to kill off my existing T cells and make space for my new supercharged ones. The chemo took three days and was given on the haematology day unit. I had no major side effects other than a lot of fatigue. I then had a rest day before being admitted to the haematology ward the next day. Nothing happened on the day of admission, it was just settling into the room and a few blood tests. Then the real CAR-T therapy fun started:

Day 1 (Monday)

At 8am, I was taken for an MRI brain scan. This was just to be used a reference in case I later developed any neurological side effects which are common with CAR-T.

At about 11am, the T-cells arrived in the room accompanied by some folks from the hospital’s stem cell lab, who supervised their administration.

The CAR-T cells were given back to me via my central line. There was a slight taste of chemicals as they went in but there were no other side effects. The infusion was very small and only took about 15 minutes. It was all a bit anticlimactic given everything that had gone on in the weeks prior.

The nurse monitored me every 15 minutes for a couple of hours, but I had no reactions so this was reduced to every 4 hours. As well as the standard blood pressure and temperature observations, I had to have regular neurological assessments. These involved answering a set of standard questions, counting backward from 100 in tens, and writing out a standard sentence. These were repeated every 4 hours for the next 30 days.

Day 2 (Tuesday)

Day 2 was very uneventful. The assessments continued but I had no reactions or side effects. So far, so boring. I wasn’t allowed to leave the room but thankfully, I’d brought a portable projector and a VR headset to keep me entertained.

Day 3 (Wednesday)

I woke up with sore throat but I was otherwise ok and my blood results were not concerning. My temperature crept up during the day and I started to feel more lethargic and malaise. By 6pm, my temperature had reached 38oC, which was caused by Cytokine Release Syndrome (CRS).

CRS is a side effect that affects most CAR-T therapy patients. It’s caused by the modified T cells releasing a chemical messenger (cytokines) that signal other cells to multiply. It is graded 1 to 4, with 4 being the most serious and requiring intensive care. It often resembles a serious infection with temperatures, shivers, aches etc. However, it can also cause neurological symptoms, including confusion, seizures and loss of consciousness.

The hospital follows a strict protocol for CAR-T therapy. My temperature of 38oC was considered grade 1 CRS, so I was examined by the doctor and treated with IV antibiotics and IV Paracetamol. Blood cultures were taken from my arm and from my line (these were all negative). I also had a chest X-ray, which was clear.

Day 4 (Thursday)

My temperature was slightly elevated in the evening (37.5oC) and I was given oral Paracetamol. The IV antibiotics continued. I began feeling more and more lethargic and malaise.

Day 5 (Friday)

I continued feeling lethargic and malaise with a slightly elevated temperature of 37.8oC in the evening, and I also developed mild diarrhoea. The oral Paracetamol and IV antibiotics continued and the blood cultures were repeated (and again were negative).

Day 6 (Saturday)

My temperature was still elevated and I was still feeling very tired and poorly. I slept most of the day. I developed a bit of a cough but a chest examination was clear. The oral Paracetamol and IV antibiotics continued.

Day 7 (Sunday)

My temperature was still spiking and I was still very sleepy and didn’t feel like getting out of bed at all. Oral paracetamol and IV antibiotics continued and the blood cultures repeated.

Day 8 (Monday)

Again I was very tired and sleepy and I now had a thumping headache whenever I moved. My temperature rose above 38.5oC, which was the trigger for stage 2 CRS. At stage 2, the protocol dictated that I was given Tocilizumab, a drug that dampens down the immune system, reducing the effects of the CRS. It didn’t immediately improve my symptoms, so I continued on IV paracetamol and antibiotics.

I had another chest X-ray which was again clear.

Day 9 (Tuesday)

By now the Tocilizumab was kicking in and I was starting to feel a bit better and have more energy. My temperature reduced to 37.4oC. I continued on the IV antibiotics.

Day 10 (Wednesday)

I was feeling pretty much back to normal and had no temperature spikes during the day. A mild temperature spike in the evening 37.5oC was treated with oral Paracetamol and the blood cultures were repeated. I continued on the IV antibiotics.

Day 11 (Thursday)

I was feeling more energetic and had no temperature spikes. The antibiotics were stopped and I was monitored for 24 hours.

Day 12 (Friday)

I was feeling ok and the doctors were happy to discharge me. My partner had to continue doing temperature and neurological assessments three times a day. The CAR-T specialist nurses phoned me every day to check on me, and I visited the outpatient department weekly to see the doc and have my line dressing changed.

I’m now on day 21 and continue to be fine. The next major milestones will be the 1-month and 3-month PET scans, which will show whether or not the CAR-T cells are working. The doctors have explained that it’s normal to still see some disease on the 1-month scan, but if the treatment is working, there shouldn’t be any progression 🤞

Preparing for CAR-T Therapy

When my lymphoma relapsed, the plan was to try a stem cell transplant. For the transplant to work, I had to be in remission. So, I had 2 cycles of R-GDP chemo, followed by a PET scan. The PET scan showed a mixed response. Much of the lymphoma had disappeared but one node in my chest had grown. Unfortunately, this meant the chance of the stem cell transplant curing the lymphoma had dropped to around 20%. Rather than continue with the transplant, we decided to try for a new type of immunotherapy, CAR-T therapy.

CAR-T therapy is a revolutionary new cancer treatment that involves genetically modifying a person’s own immune system to fight cancer. Most other treatments only work while you’re having them, but CAR-T is a living treatment. So, it stays in your body fighting the lymphoma. Amazing! But it’s not without its issues.

CAR-T therapy is complex, very very expensive, and risky. Around 5% of patients die from the treatment and 25% end up in intensive care. The cost per patient is over £280k and there are only a few labs that can manufacture the CAR-T cells. So, the NHS only make it available to lymphoma patients who’ve had 2 previous failed lines of treatment. Hospitals can’t make the decision to give CAR-T themselves, a national panel meets weekly to consider potential cases. This meant a short but agonising wait to hear whether or not I would be given the treatment. Thankfully, I was and preparations for the treatment started straight away.

CAR-T is a very demanding treatment, and I had to be fit enough to have it. This meant a lot of tests! In the weeks leading up to treatment I had an ECG, echocardiogram, pulmonary function test, chest X-ray, PET scan, 24-hour urine analysis, physical examination and lots of blood tests and swabs.

The treatment is based around T cells. These are the part of the immune system that patrol the body looking for and destroying cells that have been damaged or infected. However, cancer is good at evading this natural defence mechanism and so the T cells aren’t able to recognise the cancerous lymphoma cells. CAR-T therapy works by inserting some extra instructions into the DNA of the T cells, which enables them to spot and then destroy cancerous B cells.

Unfortunately, it’s not yet possible for CAR-T cells to distinguish between healthy and cancerous B cells, so the treatment kills all of the B cells. This isn’t too much of a problem for lymphoma, as it’s possible to live just fine without B cells and drugs can be used to plug the gaps left in the immune system. However, it means CAR-T can currently only be used for a small number of mostly blood cancers. ¹.

The treatment works by first extracting a patient’s T cells. These are then sent to a lab (in my case they were flown to America) where they are genetically modified before being given back. I was offered a choice between two different types of CAR-T. I opted for Yescarta, which has more intense side effects and slightly higher risk of death but also has a slightly higher chance of achieving a lasting remission. In studies, about 40% of CAR-T cell patients go on to achieve lasting remission.

Connected to an Aphesis machine collecting T cells for CAR-T therapy — Having T cells collected with an aphesis machine

Collecting the cells happens through a process called aphesis and it was painless. Blood was taken out through a central line that I’d had inserted a couple of weeks earlier. The aphesis machine then separated out the T cells and pumped the rest of the blood back in. It took around 5 hours to collect enough of my cells.

Once the cells arrived back, the treatment could start.

References

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BBC News – ‘Living drug’ offers hope to terminal blood cancer patients

Having a PICC line/central line

As chemo involves lots of blood tests and intravenous medicines, it’s common to have a semi-permanent PICC line or central line implanted to make these easier and to reduce the number of needles and cannulas needed. As an example, in one of my chemo sessions, where I didn’t have a line installed, had to be abandoned after 7 attempts to get a cannula in my hand failed.

There are different types of lines. I had a PICC line for my first type of chemo (DA-EPOCH-R). For my second type (R-GDP) and my CAR-T therapy, I had a Tesio central line fitted.

PICC lines (Peripherally Inserted Central Catheter)

PICC lines run from your arm to a large vein near the heart. The installation of my PICC line was very straightforward. A specialist nurse on the haematology day unit did the installation. The vein in my arm was located using an ultrasound machine. I was injected with local anaesthetic and the line was then inserted. It wasn’t painful and took about an hour.

The line had to be flushed and the dressing changed weekly. My CNS did this for me in the clinic. My line occasionally got blocked, but the nurses had a procedure that dealt with that.

Getting the dressing wet loosens it and can lead to infection. So, there was a lot of trial and error involved in learning how to shower with the PICC line. Despite what the internet says, don’t use cling film, it doesn’t work at all! I bought this PICC sleeve, which was brilliant.

Having the PICC line removed wasn’t too bad,there was a little bit of pain as the clamp was removed but otherwise, it was ok. I have a very small scar on my arm where the line was.

More information on PICC lines are available on the Macmillian website.

Central lines (tunnelled central venous catheter)

Central lines generally go into the chest rather than the arm. There are various types of them and you’ll often hear them referred to by the brand names Hickman, Groshong or Tesio.

Tesio central line shortly after insertion

Currently, I have a Tesio Line. This type of line was created for dialysis patients, but it’s used in people having stem cell transplants and CAR-T therapy as the process of harvesting the cells is similar to what happens during dialysis.

The implant procedure for the Tesio line was much more involved than a PICC line. Whereas my PICC line was done on the day unit by a specialist nurse, the Tesio line was done by a full operating theatre team led by a radiologist. The procedure was very uncomfortable but not painful. It took about 45 minutes, but I was in the department for 4 hours for observations, waiting etc.

They have a preference for installing the line on the right side of the chest, but it all depends on how your veins are, which will be examined by ultrasound before the procedure starts.

The day following the insertion of the line was difficult. The dressing applied to the insertion site near my collar bone was very tight, this was to stop any bleeding. However, this made any movement in my neck painful, and even swallowing was uncomfortable. The next day it was back to the haematology day unit for a dressing change. This made things a lot more comfortable, though I was still sore for several days afterwards. A couple of stitches were used to close the insertion site, these were removed 10-days afterwards.

A tip, if you have chest hair shave it, all of it, before having the procedure. I shaved the hair on my pecs but not in between them, which was a mistake as the lumens of the catheter were taped to the middle of my chest. The dressings they apply are quite large and pulling them off chest hair is hell!

My experiences living with lymphoma

Life before lymphoma

Hi, my name is Paul. I’m a PhD researcher in AI with a love of nature, science and snowboarding. In October 2021, at the age of 40, I was diagnosed with stage 4, double-hit lymphoma (a rare and aggressive form of blood cancer). This is a blog of my experiences of living with and being treated for lymphoma.

Important: I’m not a doctor. This blog is just about my experiences as a patient. Don’t take it as medical advice. Haematologists, Clinical Nurse Specialists or organisations like Macmillian or Lymphoma Action are much better sources of advice about treatments, risks, side effects etc.

Getting a diagnosis

The worst part of the whole thing so far was waiting for a diagnosis and for treatment to start. My initial symptoms were intermittent stomach pains that gradually became more constant and painful. I had a fast-growing lump in my abdomen and although I’d seen my GP and been given a 2-week referral to the hospital, the pain became so great I ended up going to A&E.

At A&E I was given a CT scan which showed several enlarged lymph nodes and that the lump in my abdomen had grown to 10cmx15cm (about the size of a grapefruit). At this point, the doctors told me that they suspected lymphoma. They discharged me with Oramorph to manage the pain and scheduled a biopsy and referral to haematology.

What followed was 6-weeks of agony as my symptoms got worse. The lump got bigger and the cancer spread throughout my body. By the time of the PET scan, about 2-months from the start of initial symptoms, the lymphoma had spread from my abdomen to my neck, lungs, and kidneys. I was stage 4BEX. The B means I had night sweats; the E means the lymphoma had started outside the lymphatic system, and the X means that I had “bulky disease” (i.e. a very large mass in my abdomen). Lymphoma is staged differently from solid cancers, Lymphoma Action has a great guide to the staging of lymphoma.

Initially, my diagnosis was high-grade B-cell lymphoma, but after further analysis of the biopsy, this was changed to double-hit lymphoma.

What is double-hit Lymphoma?

Double-hit lymphoma (DHL) is a rare subtype of non-Hodgkin lymphoma, making up only about 5% of B-cell lymphomas¹. Unlike most lymphomas, in which the cancerous lymphocytes have only 1 genetic mutation, double-hit lymphoma has 2 mutations.

DHL is a very aggressive (fast-growing) blood cancer and is more difficult to treat than standard B-cell lymphoma². It is also more likely to relapse and more likely to spread to the central nervous system. Despite being more difficult to treat than other lymphomas it is still curable and new treatments are becoming available, like CAR T-cell therapy.

The WHO only classified it as a separate type of lymphoma in 2016. And so, doctors and researchers are still learning the best ways to treat it.

Medically it’s referred to as “High grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6”.

Treatment for double-hit Lymphoma

The standard chemotherapy for B-cell lymphoma (R-CHOP) is not very effective against DHL, so more intensive treatments are used. In my case this was DA-EPOCH-R.

Because of the risk of central nervous system involvement (i.e. it going to my brain), I also had intrathecal and high-dose IV methotrexate.

The treatments appeared to be successful and by my third cycle of chemo, the PET scan showed complete metabolic remission (i.e. there was no sign of active lymphoma). I still had some “residual mass” at the original site in my abdomen, but this was “PET negative”, meaning it was just a collection of dead cells and scar tissue with no active cancer cells. I had another PET scan after my sixth cycle of chemo, again this showed complete metabolic remission.

Because of the risk of relapse, I also had radiotherapy as “consolidation”.

Remission and Relapse

After 11 months of treatments, it was wonderful to be in remission and have my old life back. I’d worked hard to regain my fitness levels, started back at work, and started socialising again. Unfortunately, it wasn’t to last and after only 2-months, I relapsed. The plan at this point was to have an autologous stem cell transplant. This required more chemotherapy, this time with the R-GDP regime, to get me back into remission (this is known as salvage chemotherapy). Unfortunately, the salvage chemo failed and my lymphoma was still growing after 2 cycles of it. So, my consultants advised abandoning the stem cell transplant and trying CAR-T therapy instead.

I had the CAR-T therapy in November 2022, and I’m now waiting to see whether it’s working.