I have been selected to be a participant in a clinical trial
called “A Phase 1 Study of bb2121 in BCMA-Expressing Multiple Myeloma”. Hooray!!!
Let me riddle out that title for you. A Phase 1 study is primarily intended to
assess side effects of a drug or procedure, and to identify the optimal level
of dosing. If the treatment works, that
is just a bonus, not the intended outcome.
The Phase 1 study I am joining has been underway since January,2016, so
I am a late stage participant, which means I will get a higher dose of the
treatment.
BCMA-Expressing Multiple Myeloma. BCMA stands for B-cell maturation antigen.
That is a protein that may exist on the surface of a myeloma cell. My myeloma cells have been tested, and they
do have BCMA on their surface, so they are BCMA-expressing.
Bb2121 is more complicated.
Bb2121 is a chimeric antigen receptor T cell therapy (CAR-T) targeting
BCMA. T cells are a kind of white blood
cell that mature in the thymus and help target or destroy foreign or invasive
cells. Chimeric antigen receptor means a
mechanism for identifying a particular type of antigen, in this case the BCMA
antigen. My T cells do not naturally
have the ability to identify the BCMA antigen.
The process of adding bb2121 to my white blood cells is
interesting. At the hospital they
extract my white blood cells through a process called leukapheresis. The white blood cells are shipped off to a
company called Bluebird Bio, Inc. At the
“factory” they first cause the T cells to multiply. Then they use a lentivirus to insert a gene
into the T cells that will recognize the BCMA antigen. Then they further cause the modified T cells
to multiply until there is a sufficient amount (or more) for my treatment. Finally they ship the activated T cells back
to the hospital where they are infused into my blood stream to attack any cells
with BCMA on their surface. The process
from extraction to re-injection takes about 4 weeks.
To qualify for this study you must have relapsed and
refractory Multiple Myeloma. Relapsed
means you have Multiple Myeloma that has come back a number of times. Check, I have. Refractory means you have received prior
lines of treatment that have become ineffective. Check, that I have also. The original treatment of Velcade, Dexamethasone,
+ Revlimid became ineffective this spring.
The antibody treatment I received in August & September,
Daratumumab, was initially effective, but at the end proved ineffective. The replacement treatment of Carfilzomib, Dexamethasone,
+ Pomalyst has not proved to be totally ineffective, and I have only received
it for 2 rounds of treatment, but it has not been the revolutionary treatment
that it is reputed to be.
So the idea is that I will receive my modified T cells back
after they have been “weaponized”, and they will search out and destroy my
Multiple Myeloma cells. In the past they
have said they had no way to cure Multiple Myeloma, but they could control its
effects and make it a chronic condition.
If this treatment actually does destroy all the Multiple Myeloma cells,
that certainly sounds like a cure to me.
Dr. Levine, my oncologist, warns that this treatment is very new, and
they need years of results to fully appraise the effectiveness of a
treatment. Could whatever caused the
Multiple Myeloma in the first place happen again, and reintroduce the
disease? Yes, but you hope that there
are weaponized T cells lying around that could destroy those cells as
well. Could there be pockets of Multiple
Myeloma cells that the CAR T cells don’t find?
Certainly. But the results in
other blood cancers currently being tested, such as certain forms of leukemia,
are very positive. 90 – 95% have had complete
remission and have stayed that way for a year.
Since most recurrences of cancer happen in the first 2 years, that is
very hopeful.
What are the side effects of the treatment that the Phase 1
study is designed to assess? Two that
stand out are CRS and Neurologic toxicities.
I always thought CRS was an affliction of the elderly standing for
“Can’t Remember Shit”. That may be, but
CRS in this context means Cytokine Release Syndrome. It occurs when the modified T cells kill so
many Multiple Myeloma cells that the waste products that result from the cell
deaths overwhelm the body’s ability to remove them, resulting in fevers,
chills, low blood pressure, shortness of breath, and lots of other pleasant things. They keep you in the hospital for 21 days to
monitor and evaluate you. They have ways
of treating these side effects, but the key thing they want to observe is how
my response lines up with the dosage I receive.
Neurologic toxicities are side effects associated with the
brain: confusion, disorientation, sleepiness, hallucinations, tremors, seizures
and difficulties with speech and balance.
In my case, how will they know?
Apparently they have a variety of subjects, so they have a plan. They will establish a baseline before the
treatment for a number of exercises that will cover these possible side
effects. Then they will do those same
exercises after the treatment. Any
changes will alert them to possible neurologic side effects.
All of this results in a commitment longer than the stem
cell transplant I underwent back in 2012.
I recall that I got out of the hospital after 11 or 12 days. This requires a 21 day stay in the
hospital. But presumably the impact is
much less. I was wiped out and slowly
recovering for months after the transplant.
Ideally, with the Multiple Myeloma gone, I will be substantially better
after this event. At least that is my
fervent hope.
All this depends on my remaining healthy enough during the
next 7 weeks so that I can participate in the study. The coveted slot in the study opened up for
me because another participant caught a cold.
Avoiding colds at this time of year in New England is difficult,
especially at this holiday time, which of course I hope to spend with those
little germ vectors known as grandchildren!
It now becomes a waiting game during which the goal is to remain healthy
enough for the process described above to begin.
