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 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.
Clearly my CLL is on the march
in the blood, marrow and nodes and it is time to treat.
So 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
suggestion 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 a chance 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.
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 will
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 leaves is that I am predicting a
great final outcome but am buckled up for the fight of my life ahead of my
restaging one month post CAR-T infusion
Looks like I will need to get worst to get better.
Wish it weren’t so but it is what it is. I say bring it on.
Stay strong.
We are all in this together.
Brian
