Double Hit Lymphoma Archives - Living with Lymphoma

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

1
BBC News – ‘Living drug’ offers hope to terminal blood cancer patients

Having chemotherapy with DA-EPOCH-R

The principal treatment for my double-hit lymphoma was chemotherapy. The standard chemotherapy regimen for B-cell lymphoma, R-CHOP, is not very effective at treating double-hit lymphoma. And so, I was treated with a more intensive regime called DA-EPOCH-R. The name describes the components of the regime:

DA – Dose Adjusted

Unlike other chemotherapy regimes, the dosage of drugs changes during treatment with DA-EPOCH-R. The doctors looked at my blood tests during each cycle and, depending on the results, increased the dosage in the next cycle. As I coped relatively well with the treatment my dose increased with every cycle.

EPOCH

EPOCH refers to the chemotherapy drugs given in the treatment. They are Etoposide, Prednisolone (a steroid), Vincristine (aka Oncovin), Cyclophosphamide, and Doxorubicin (aka Hydroxydaunorubicin).

R

This refers to Rituximab, an immunotherapy drug that kills B-cells.

How DA-EPOCH-R is given

I had 6-cycles of DA-EPOCH-R with each cycle lasting 3-weeks. Whereas many other lymphoma regimes can be given in a day, it takes 4/5 days to administer DA-EPOCH-R. In my case, this required a hospital stay for each cycle.

I had Prednisolone tablets each day. Etoposide, Vincristine and Doxorubicin were all given together as an IV over 96 hours. The Cyclophosphamide was given as a bolus (an injection) at the end of the treatment; it only took about 10-15 minutes.

Hooked up to DA-EPOCH-R chemotherapy — Hooked up to DA-EPOCH-R with a lovely birthday cake from the nurses.

Rituximab was given by IV, sometimes at the beginning of the treatment, and sometimes at the end. As it causes a reaction in some people, I had an IV antihistamine immediately before it. The first time I had Rituximab, it was given at a slower rate, once the nurses were confident that I wouldn’t react to it, they increased the rate. At the faster rate, it took a couple of hours to administer.

I had a PICC line fitted before the treatment started. But unfortunately, because the chemo took up both lumens of the PICC line, I still had to have daily blood tests done with needles.

Effect on my lymphoma

DA-EPOCH-R worked remarkably well on my lymphoma. Within a few days of the first treatment the visible lumps I had started to go down. By the end of the second cycle, all the visible lumps had disappeared and the pain had reduced a lot.

I had a PET scan at the end of the third cycle, which showed complete metabolic remission (i.e. there was no sign of active lymphoma). There was still 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 was given another PET scan after my sixth cycle, which again showed complete metabolic remission.

Ultimately though, DA-EPOCH-R wasn’t able to completely get rid of my lymphoma and a few months after finishing treatment, I relapsed.

Side effects of DA-EPOCH-R

DA-EPOCH-R is an intensive treatment regime and the side effects are equally intense. I faired relatively well but still had some horrible side effects:

Fatigue

This was by far the worst side effect. I always tried to do a bit of exercise every day, no matter how bad I felt, but there were some days when I just couldn’t do anything at all.

Mucositis

From the third cycle, I started to have problems with mucositis (mouth sores and saliva changes). During the fifth cycle, I had to be hospitalised as I couldn’t eat or talk due to all of the mouth sores.

Peripheral neuropathy

Vincristine is known to lead to peripheral neuropathy. It caused numbness in my feet, which was not much of a problem during the day, but it often got worse at night when the pins and needles would start.

Weight Loss

Weight loss was a real problem for me, especially in the first couple of months of treatment. At one point, I lost 12kg and despite eating 4,000 calories a day I wasn’t putting on weight. A lot of this was due to the huge volume of lymphoma breaking down and I was gradually able to put on weight later in the treatment with the help of the hospital dietitian.

Hair loss

Pretty much all my hair fell out, including my eyebrows, eyelashes and body hair.

Chemo rash

An unexpected side effect was a large pimply rash on my forehead, cheeks, and nose. This seems to be a fairly uncommon reaction and the doctors were a bit puzzled by it. They swabbed it to make sure it wasn’t shingles. It would go down between cycles and it disappeared completely a few weeks after treatment finished.

Infection

Both the chemotherapy and the lymphoma lowered my immune system, so I had to be very careful to be as hygienic as possible, avoid crowds and people with sniffles, and monitor myself for signs of infection. I had strict instructions to phone the 24-hour haematology triage line if my temperature rose above 37.5c. I also had to carry a haematology alert card explaining my condition.

Thankfully, I was spared many of the other chemotherapy side effects. Macmillian has lots of information about other possible side effects.

Supporting medication

Alongside the chemotherapy, there were a lot of supporting medications that I had to take:

Aciclovir	An antiviral for herpes viruses, such as shingles, which can reactivate when your immune system is low.
Allopurinol	Lymphoma cells can break down quickly when treatment starts, which can cause uric acid to build up. Allopurinol helps clear this.
Ciprofloxacin	A prophylactic antibiotic
Co-trimoxazole	An antibiotic
G-CSF	Granulocyte-colony stimulating factor – an injection that stimulates the production of neutrophils.
Fluconazole	An antifungal
Metoclopramide	Anti-emetic (reduces nausia and vomiting)
Ondansetron	Anti-emetic (reduces nausia and vomiting)
Omeprazole	Reduces stomach acid and helps protect the stomach from all the other medicines.
Painkillers

I also had treatment with Methotrexate during the DA-EPOCH-R because of the risk of the lymphoma spreading to my central nervous system.

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.