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DAY 4: Entering the High Risk Zone with CAR-T therapy: Why did I do this in the first place?

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MARCH 26, 2018

I am four days past my CAR-T infusion and a week past my chemo to reduce my lymphocytes to allow the CAR-Ts to be gracefully accepted into my body and to grow to do their work.

This is around the nadir for my low blood counts from the effects on the chemotherapy on my bone marrow. And it is the beginning of the highest risk time for Cytokine Release Syndrome (CRS) that happens when the CAR-Ts start their serially killing.

This is dangerous time. My counts are still pretty good, but dropping. No fevers. Vital signs are good. So I am confident I can weather the upcoming storm, but people die from CAR-T therapy.

So why did I choose this as my next move when it became clear that I had to do something for my chronic lymphocytic leukemia that was progressing on ibrutininb. Surely there were less risky options.

And why this choice with conflicting advice from doctors that I deeply respect and with the understanding this is a treatment, as Dr. Castro says is in the flip-phone phase. Our knowledge has huge gaps that leave many critical decisions to the “art of medicine” and too many questions unanswered.

As Dr. Maloney, said CAR-T therapy is not for the faint of heart.

So when I had other choices, when I could have tried something else and tried CAR-T later when it was better understood and perhaps less dangerous, why fly up to Seattle for such an experimental therapy?

What follows is only my opinion, my thought process.

There are other strong options out there and we are all different in how we make decisions and the unique nature of our CLL.

So let’s look at my other choices.

I doubt any monoclonal antibody would help me because of my NOTCH1 mutation. Not everyone agrees that NOTCH1 matters, but there is data that says it confers a poor response rate with rituximab and ofatumumab. May not be the case with obinituzumab, but I suspect it will follow a similar pattern. Rituximab and ofatumumab had stopped working for me years ago.

I don’t have a C481 mutation that prevents the binding of ibrutinib. Instead I have a downstream gain of function mutation in PLG2 conferring my resistance. Thus it is less likely the SNS-062 or Vecabrutinib would be more effective than the ibrutinib. It is likely very helpful for those with C481.

Similarly acalabrutinib or any other BTK inhibitor in development is not likely to help. Different side effect profiles, but the efficacy would be seriously blunted by the lack of ability to bind and block the BTK receptor.

A P13K inhibitor such as the approved idelalisib has provided decent responses rates for folks like me, around 50/50. Other PI3K inhibitors in clinical trials might have be an option, but the response data for folks like me is even thinner than the CAR-T results. I might consider it downline.

CAR-T responses rate in CLL are closer to 80% so I prefer it now.

Immune modulating drugs such as high dose steroids or lenalidomide worry me because they might awake my sleeping auto immune issue, ITP where my aberrant immune system attacked my own platelets and  almost killed me a few times. Let it sleep I say. Don’t tickle it.

There are many early trials of what might turn out to real CLL magic bullets that were viable options. I wasn’t sure I wanted to risk letting my disease take off while I trying to find out whether I picked the next winner.

The promising UCSD ROR-1 mAb (cirmtuzumab) and ibrutinib trial was closed to me due to my prior use of ibrutinib. That was disappointing.

Venetoclax (V) was a strong alternative and the one that I most commonly asked: Why not venetoclax?

I think V would have been an excellent choice, especially if I stayed on ibrutinib to catch my unstable CLL in a pincer death grasp. And that is a real possibility in a clinical trial or even by prescription. And pretty affordable at least while I still have commercial insurance. I was less excited by single agent V for my CLL due to the unstable nature of my CLL cones, but the V+I combo looked mighty tempting to me.

So I waffled back and forth and finally went with CAR-T because I wanted the chance to be done with CLL and I believe a cellular therapy offered me the best odds. I wanted to se chronic lymphocytic leukemia in my rearview mirror.

For others with less evolved disease, earlier in their CLL journey, some of the combinations look pretty amazing wit deep and durable response. In my circumstances, I am less convinced. I want the disease knocked way way back and I worry about Richter’s with my profile. Less disease, less Richter’s risk,

And finally, CLL management is a chess game. If I chose V+I I would have likely gotten a good deep response, but if I started to progress in a year or two, there is no certainty that there would be an appropriate CAR-T trial for me. There is no guarantee that Medicare would pay for it if was approved. a long shot.

The timing felt wrong.

If I fail CAR-T, (I don’t think I will), then I could alway jump to V+I in or out of a trial.

Like a chess game, I was thinking a few moves ahead.

Better to have two good moves than one.

5 Responses

  1. Hi Brian, just wanted to check-in and catch up on how you are doing. I just read all of your blogs leading up to today. I am glad you finally answered the question in detail of ‘why this trial, rather than some other, now’? I know you had other choices. Also appreciate the other info about what it’s like to go on CAR-T. As I’ve said before, I too think that’s the future for just about all of us. I am deeply appreciative of your bravery and courage in stepping forward to move the medical world one step closer to a cure. I also enjoy your conversational writing style… makes it very easy and fun to get caught up. I wish you the best, my friend, and you are in my prayers. I pray you are one of the first to be fully cured of CLL!


  2. Dear Brian,

    I’m thinking about you every day and wishing you a road to wellness quickly with ZERO CLL when all is done.
    Your strength is amazing; you are truly an inspiration with your bravery to help yourself and others along this scary path.

    Sending lots of love and prayers to you, Patty and your family.

  3. Thank you Brian for explaining your decision. I was wondering why you didn’t try Venetoclax with Ibru or Obin and your reasoning makes sense to me. I’m thinking of you and hoping you get a great result from CAR-T. Thank you for all the information you share with us and for taking this brave step.

  4. Your reasoning makes complete sense. I’ve just finished reading your blog from April 1st and hoping that your fatigue and headaches subside.

    Wishing you all the best,


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