I had planned to write more often, but long hospital days, followed by long naps and long walks most days have precluded me doing much more than remembering my trial schedule and completing a hurricane of critical paperwork and lengthy CLL Society’s to-do lists while I am still able to work.
Despite my sincere intention to be here and now in a more public way, blogging has taken a second seat to more mundane needs. And to my own health priorities like sleep and exercise.
But I have my clinical studies to share now.
Two days ago, I got my results, and the news was mixed.
My blood chemistries were all good except for a slightly elevated LDH consistent with a cancer on the move.
My blood count showed a continuing slow downward trend in my HGB (today it was 11.9) and a slightly climbing lymphocyte count in the high teens now. Platelets and neutrophils remain within the normal range.
Just a few months ago my lymphocyte count was 1 and HBG was 14. My CLL is taking off.
Bone marrow biopsy (BMB) was hypercellular at 65% suggesting it has had to expand due to infiltration with leukemic cells. In fact it showed that more than 80% was filed with lymphocytes, leaving less than 20% of the factory floor to make all my red cells, platelets and other white cells.
By flow cytometry about half of the white cells were clonal, consistent with CLL.
The one surprise was that no 17p or 11q deletion was detected Hard to explain. May be a sampling or technical error, or that a different CLL sub-clone without those deletions has become predominant in my marrow.
My last BMB five years ago had normal bone marrow cellularity at 40% and only 20% was lymphocytes. That was on ibrutinib while it was working well.
My CT scans last week were filled with” innumerable” enlarged lymph nodes, but at least they were all less than 4 centimeters in their longest diameters.
My PET scan showed those nodes to be metabolic active, but the highest SUV was only 4 making Richter’s Transformation (RT) less likely. However, PET scans may be less helpful in predicting RT in those failing novel therapies.
For comparison, two and half years ago, I had no enlarged nodes with imaging. No prior PETs in the last 10+ years.
Clearly my CLL is on the march in the blood, marrow and nodes and it is time to treat.
That’s why I am in Seattle.
Here is where Goldilocks comes into play.
If one’s CLL “tumor burden” is too high, especially if one has “massive” lymph nodes greater than 5 cm. and certainly greater than 10 cm. there is early data that suggests that the army of CAR-T cells may have too many enemy combatants to wipe out or they may be too far out of reach, even for these hyped-up serial killers.
If one’s tumor burden is too low, there is reason to believe that the genetically reengineered cells won’t get enough stimulation to expand and will just die off without ever engaging in battle.
So there is a sweet spot, Goldilocks’ just right bowl, where the T-cells are stimulated to expand but are not overwhelmed by the amount and depth of the cancer. The way T cells kill is up close and personal. They need to wrap their arms around their targets, and if they can’t get right up against each and every CLL cells in a massive node, the cancer will live on.
In fact, published CAR-T responses tend to better in the blood and marrow than in the nodes.
The good news is that my odds of a deep and durable response are excellent based oy my labs and imaging.
However, the risk of cytokine release syndrome (CRS) and neurotoxicity may also be correlated with the total amount of disease burden (not so much the size of any one node, but the sum of the diameters of all the nodes), and by that criteria, I have more than enough disease to suggest I have a wild roller coaster ride ahead of me.
While this is an evolving science and all of the data are immature, especially in CLL, the way I read the tea leashes me predicting a great final outcome but being buckled up for the fight of my life sometime in the weeks post CAR-T infusion and ahead of my restaging one month later.
Looks as if I will need to get worst to get better.
Wish it weren’t so but it is what it is. So I say bring it on.
We are all in this together.
Brian, your blog posts are profoundly inspiring. I was glad to see that you have been able to take advantage of the many lovely sites in Seattle. In 1998 I was in Seattle for several weeks for a difficult stem cell harvest at the Hutch. I was forbidden to use public transportation or to visit indoor attractions, so I walked. I walked miles every day, crisscrossing the city, visiting many of the places you have mentioned.
Please continue to blog when you can, but also know that even when you don’t feel like blogging you are ever present in my mind and heart! Beth in Tennessee, USA
So glad you are doing well 20 years later!
DR. Brian- I am so glad that the blood results indicted no 11q or 17p! That is EXCELLENT!! I am also so very happy to learn that your overall condition is favorable for CAR T-cell treatment and it appears probable that this treatment will give you a very effective and durable response. I know that people at the University of Pennsylvania have done a lot of work on CAR T-cell therapy, but I believe yours is a slightly different one- the so-called “Juno” therapy (??). What’s the difference? Are they both effective? Is one more applicable and effective than the other? Whatever the case, I am keeping you in my thoughts and prayers… and praying for an excellent outcome of all this. Stay strong, stay focused. Keep the faith, my friend… We’re all praying for you… and don’t forget- your Guardian Angel is always right by your side… -Gene Pisasale
All CAR-T are different depending on the construct. It is complicated and I don’t understand it all, but the JUNO JCAR-14 used here has a slower time til it starts growing after re-infusion and might be gentler, but no less effective. It’s all very earlier.
Sounds like you have a formidable fight but the end result can be worth it — you need lots of prayers to help you and your doctors along this rocky road — I’m definitely on your cheer squad. So grateful for your courage in choosing this path and keeping us all abreast of your trip — worth so much to all of us. You’re a special man Brian Koffman and the gift you are sharing with all of us is so valuable – can’t even begin to put into words my feelings about this. God bless you and keep you safe through this difficult time.
I visited the Irvine CLL support group for the first time this month as a new diagnosis. I think we spoke to you on speaker phone? I am a peds RN with no oncology experience, so I know enough to be scared but not enough to feel reassured. I am learning though. Having a physician in “the club” with me is extremely reassuring and I wish, pray and cheer you on this latest endeavor. I have a son at UW!