TL/DR: not dead yet!

I’ve just had my latest bone marrow biopsy results which show the percent of Leukaemia cells detected in my bone marrow.

A quick recap. In April, after my March biopsy, I was told I was in molecular relapse. The result was 0.5%.

They immediately increased my dosage of Ponatinib to the full dose - 45mg. My doctor explained he expected that Ponatinib may be slowing down the cancer growth but it isn’t stopping it.

Shortly after my last post I got approved for a new drug on clinical trials. This new drug - Asciminib - arrived a couple of weeks ago after this latest bone marrow biopsy was taken. Therefore the latest results reflect the increase in Ponatinib, not the switch to Asciminib.

The latest result shows my Leukaemia is now at 2%.

This obviously isn’t great - a fourfold increase in 8 weeks, but it’s much less than what I was fearing.

In fact, I went back and looked at the results from the December biopsy. That was 0.003%. A rise from 0.003 in December to 0.5 in March represents a 167x increase. If you project that growth forward to today… well, I’d probably be gone.

I’ve been getting blood tests every 2 weeks - each time with a sense of dread regarding the white cell count. An increase in the white cell count is an indication that the cancer is no longer consigned to the bone marrow and has now spilled into the bloodstream. This typically happens when the percentage in the bone marrow is above 5-10%, although this is an average - for some people it’s less, for some it’s more. When this happens, this is considered hematologic relapse - a tipping point marked by rapid disease growth, a fast breakdown in general health and a heightened risk of spread to the organs.

Each subsequent blood test with a normal white cell count has given me relief, and hope, that it isn’t spreading as fast as I feared.

While it’s consigned to the bone marrow, there is still a risk of what’s known as sanctuary site spread - progression to the central nervous system and testes. This is not common, but it’s not rare either. I need to carefully look out for the symptoms. The problem with this, of course, is that I’ve already been experiencing many of the symptoms due to previous treatments and current medication.

Asciminib

Understanding all the terms and different treatments is challenging for us non-medical professionals. At this point, I’ve pretty much gone through the full gamut of treatment options, so my knowledge is rapidly improving.

It started with chemotherapy. This targets and kills rapidly dividing cells, but also kills healthy cells. As I was in Australia, I had the Hyper-CVAD chemotherapy protocol - high intensity chemo that resulted in prolonged hospitalisation. If you read my previous posts you know the effects, it wasn’t nice. The NHS takes a different approach. If I had been in the UK I wouldn’t have gone through all that. Whether the end result would have been different or the same, I’ll never know.

I then had a stem cell transplant after returning to the UK. The stem cell transplant attempted to replace my cancerous bone marrow with healthy donor bone marrow. The goal is to get to 100% chimerism - where all donor cells replace my cells. I only ever got to 99%. The tiny amount of residual Leukaemia in that 1% resulted in relapse.

After relapse, I had CAR-T therapy, which is immunotherapy rather than chemotherapy. This is a type of personalised cell therapy where my T-cells were genetically engineered in a lab to recognise and kill cancer cells.

Between chemo and the stem cell transplant, I was given Dasatinib. Following the stem cell transplant I was on Ponatinib. Now I’m on Asciminib. This is not chemo or immunotherapy. These are all what’s known as tyrosine kinase inhibitors (TKIs).

I have an aggressive form of Leukaemia called Ph+ ALL-B (Philadelphia chromosome-positive acute lymphoblastic leukaemia), which involves an abnormal gene called BCR-ABL1 that causes white blood cells to grow uncontrollably. These three drugs - Dasatinib, Ponatinib, and now Asciminib - all aim to block that gene, but they each work in slightly different ways.

Dasatinib is a 2nd generation TKI that sits in the part of the BCR-ABL protein where ATP (the energy molecule) usually goes. It attempts to block that spot, and by blocking the spot, shut down the growth signal.

Ponatinib is a 3rd generation TKI. It’s designed to still work if the BCR-ABL gene mutates, especially the T315I mutation, which makes many other TKIs stop working. It binds tightly and has been found to work better than Dasatinib for hard-to-treat cases.

Asciminib is the next generation TKI. It works completely different from the others. It’s called a STAMP inhibitor (Specifically Targets the ABL Myristoyl Pocket). Instead of blocking the ATP site, it binds to a hidden “back pocket” on the ABL part of the protein and locks it into an “off” position. This avoids resistance that can develop with the other drugs.

Asciminib has been approved for chronic myeloid leukaemia (CML) patients but it is not yet licensed for ALL patients in the UK. I’ve been approved for clinical trials on compassionate grounds. At this point there’s very little clinical data regarding its efficacy in ALL patients. Ph+ ALL shares the same BCR-ABL1 gene mutation as CML, so in theory Asciminib can work similarly. There’s just not much clinical data to support the theory - I’m one of the guinea pigs.

Limbo

At the moment I feel like I’m living in limbo. Time is measured by gaps between blood tests and bone marrow biopsy results. My next bone marrow biopsy will be 8 weeks after I started Asciminib. Based on my own calculations, If the growth rate stays the same, it’s also about that time that the cancer could start showing in the blood results. Therefore, if my white cell count is still ok around this time then that may be an indication that Asciminib is working - either slowing the growth further, or in the best case, reversing it. I can but hope. I should get the biopsy results early August, at which point the team have a decision to make about whether to go ahead with donor lymphocytes. I talked about this in my previous post.

For now, I’m just trying to deal with the various side-effects which have changed with each treatment, and concentrate on getting stronger for what’s to come.

The last two months haven’t been great. April ended with an unplanned visit to hospital. The constipation got ridiculous, it required extreme measures. It’s fair to say I reached a new milestone - the full dose of prescribed laxatives, 8 sachets of Laxidose, three suppositories and two enemas in a 24 hr period. It did the trick, and since then I haven’t had any problems in that department.

Since then, I’ve been having various other side-effects most days to one degree or another. It’s nothing I haven’t been through before. The main challenge has been in my head.

From the beginning of this nightmare, I’ve been pretty strong mentally, but something changed in May. I just lost motivation and everything became a big struggle. I’ve had plenty of offers of help. There’s no shortage of that available - whether from the hospital or cancer charities. When I was an in-patient I had regular visits from the resident chaplain - whether I wanted it or not.

I know mental support is helpful for a lot of people but it’s not something I’ve personally sought out. I don’t see what difference it makes. I know the root causes of my issues. Any mental problems are a direct result of my physical problems. Talking about it with a stranger isn’t going to change the underlying facts. I also know that bottling it up isn’t helpful. I don’t. There’s not much else going on in my life at the moment so talking about it with those around me hasn’t been a problem. Even this blog is a form of therapy. Except, in May, I guess I did shut down and bottle things up for a while.

I think I’m through that phase now and back on the right side. I’ll probably slap the next person who tells me to “think positive”, but besides that, I am getting back to normal - getting out when I can and appreciating the now, rather than worrying about the future. Receiving the latest biopsy result has helped. It’s the not knowing that’s the hardest.

In 3 weeks I will be 50 years old. There was a time when I didn’t think I’d make it to that milestone. I’ll take that as another win.