(Warning: This blog post is non-technical but purely personal. In my leukemia diary, I write openly about my current health issues. This blog might be triggering for people who struggle with, or lost dear ones to, cancer and other similar diseases.)

Last week, my near future was clear. I would go through the official entry tests for the CAR-T trial. Hopefully, I would pass them all, and then start on that trial. Or, if not, I would fall back to the alternative approach of azacitidine combined with venetoclax, AZA-VEN.

And then things changed. Again.

June 22

In the morning of Monday, June 22, I got a call from my Amsterdam hematologist.
“Hey, Hugo. I want to start your treatment tomorrow already.”
“Tomorrow? But what about those official entry tests?”
“Yeah, that is for CAR-T. We’re not doing that. At least not now. I want to get you started on AZA-VEN as soon as possible. Can you be here tomorrow?”
“Well, of course. Not a problem. But what happened to our plan to go for CAR-T first?”

It turns out that the CAR-T trial has a little supply chain issue. To understand this in more detail, let me first describe in a bit more detail what this CAR-T trial is exactly.

CAR T-cell therapy (Chimeric Antigen Receptor T-Cell therapy) in itself is not new. Or rather, not super new. It’s the application of CAR-T technology to AML that is really new.

So the “standard” CAR-T cell therapy means that white blood cells of the patient are harvested, genetically modified to attack the patient’s cancer cells, and then cultivated and grown until there are enough to infuse back into the patient. That approach does not work for AML, though.

The clinical trial that I was about to enter changed the approach in two ways. First, it doesn’t use the patient’s white blood cells, but that of a healthy donor. And second, the white blood cells are not modified to attack the cancer directly; instead, a supplementary medicine is given that works kind of like a bridge between the cancer cells and the genetically modified white blood cells. So one side of the supplement has a receptor that attaches to the CD123 receptor on the cancer cells, and the other side has a receptor that the modified white blood cells can attack.

Obviously, with this being a very new approach and still in very early trial stage, the manufacturer does not have huge supplies yet. As I understood it, they use the white blood cells of just a single donor (hence one of the tests I had already passed was for genetic compatibility with that donor, to prevent rejection of the donor white blood cells by my body). And their supply of genetically engineered white blood cells is very limited – if I understand things right, they currently have just a single batch, waiting for the first guinea pig … I mean patient.

That batch of genetically engineered white blood cells is constantly being tested, to make sure that the trial will actually measure the effectivity of the new CAR-T approach, and will not be tainted by injecting a patient with a defective or spoiled batch. And this is where things have gone wrong. One of those many tests had failed. Not in the sense of showing a negative result, but in the sense of there being a small error in the test, so that the result is not trustworthy. It is still very likely that the batch of white blood cells is completely okay. But that one non-conclusive test casts a doubt on the reliability. A doubt that the manufacturer does not want. So they have scheduled to repeat that one test. Sadly, this is a test that can take a few weeks.

My Amsterdam hematologist said that he does not want to sit and wait and do nothing during that period. The risk is too high that my cancer would grow, and be at a level where even CAR-T becomes pointless by the time it is available again.

June 23

And so, my wife and I once more were at the hospital on June 23. For a few standard tests (blood, blood pressure, temperature, saturation). For a long talk with the hematologist for the road ahead. And for the first application of azacitidine.

The hematologist explained that the AZA-VEN approach can basically result in three conclusions.

The most positive is that this approach has so much success that my cancer cells are reduced to a level where we can, once more, consider the stem cell transfusion that then hopefully provides the final cure. In that case, I won’t enter the CAR-T trial at all.

A second option is that AZA-VEN manages to keep my cancer sufficiently in check that, once the CAR-T trial has fixed its supply chain issue, I can enroll in that trial. Which then hopefully will manage to reduce my cancer cells even more, so that stem cell transfusion becomes an option after the CAR-T approach.

And the final, option, the one I don’t want, is that AZA-VEN does not do enough. My cancer still keeps growing, and by the time CAR-T is available again, it is already too late for me.

When asked, my hematologist estimated each of those three scenarios to be about equally likely. With, in the second phase, then a follow-up 50% chance of CAR-T doing what it needs to do to save my life. All in all, I consider this good odds. Not the odds a normal person would want. But much better odds than what I thought I had just a week ago, so I’ll take it!

After he had answered all our questions, he sent me off to get the first injection. I will have to return daily, for seven days in a row, to keep getting new injections. After that, there will be a three-week rest period. And then I’ll have a new bone marrow puncture, to assess how effective the AZA-VEN approach has been, and to determine how to continue my treatment.

June 24 – 29

From then, until next Monday, my days are mostly the same. Drive to Amsterdam, to get some blood sampled, and then get my next daily azacitidine shot. Take my venetoclax pill at dinner. Await the blood results, to see if everything is going as planned.

On Wednesday afternoon, the blood sample showed a high amount of killed cancer cells in my blood. That is good, because it shows that AZA-VEN is effective. It’s not possible to tell whether it’s effective enough. But at least we see that it works. But my blood also showed worrying values for my kidney function. This is a known possible side effect of AZA-VEN. The amount of dead cancer cells in the patient’s blood can overwhelm the kidneys. And in my case, with only a single kidney left, that is even more of a concern. The doctor told me to make sure I drink even more water than I already do, and see if that helps enough.

On Thursday, he acknowledged that my increased water intake did indeed have the desired effect. My kidney function was within safe boundaries again, and there was no reason to take any extra measures.

While azacitidine, like any chemotherapy, has a high likelihood to cause nausea, I actually still feel fine. The only slight nausea I have from time to time is from the sheer amount of water I drink!

Future?

After June 29, I will no longer get new azacitidine for at least a three-week period. The venetoclax and some other medications will continue, though. And then comes the moment of truth, when I get another bone marrow puncture, to check how my body responded, and how much cancer is left in my body.

Sometimes I wish I could speed up time! That three-week wait will, once more, feel like a much too long time of doing nothing. But I asked the hematologist, and he said that there is nothing to gain from doing a puncture before that date. So I’ll have to accept that waiting is the only option here.

I expect to write the next leukemia blog entry once that bone marrow puncture has been done, the result is in, and I know what that means for how to continue my treatment.