Treatment ON!

On September 19^th I did enter the hospital to get my CAR-T Cell treatment.  Given that my original admission date of 9/5 had been delayed by 2 weeks, Barbie and I were quite concerned that there might be additional delays.  They had done a bone marrow biopsy (BMB) on August 30^th, and we were concerned that it would not be close enough to the actual treatment date, so they would have to do another.  A BMB is not really a big deal, but it feels like is should hurt like crazy.  They numb you up enough that it doesn’t, but this last one had a residual effect that bothered me for a week.  We also were required to see a member of the Beth Israel dermatology department to check out both a rash and the growth that had been removed on 8/20 and then the site further scraped and burned on 9/4.  But what really worried us was a growth on my left arm that felt like glass shads in my arm whenever it got bumped.  But the derm said that the arm growth could be treated after the multiple myeloma and cleared me for admission.

The Wednesday of my admission they gave me what they refer to as lympho-depleting chemo.  A relatively small dose of Cytoxan and fludarabine was administered for 3 days.  The idea is to make room for the CAR-T cells later, but that doesn’t make a lot of sense to me.  I think they do it just because they have found it increases the beneficial outcomes, not because they understand why.  At any rate, they monitor you closely, but I had no adverse effects.  Then they give you the weekend to recover, which I guess I did.

On Monday, 9/24 they gave me 4 batches of my own T-cells, modified to become CAR-T cells.  CAR stands for Chimeric Antigen Receptor.  That is a feature added to the surface of your T-cell that enables it to recognize a protein expressed on the surface of the multiple myeloma cell.  Normally the multiple myeloma cell, which is a plasma cell that has undergone some mutations, looks like one of your own cells to the T-cell, so the T-cell doesn’t attack it.  The CAR allows the T-cell to recognize the multiple myeloma cell as an invader, and it attacks it.

Back in February I got 2 batches of my weaponized T-cells.  Each batch is a small plastic bag with around 75 million T-cells.  Blood cells are incredibly small.  The fluid in the bags is certainly less than half a teaspoon, probably more like a quarter of a teaspoon.  2 bags amounted to 150 X 10⁶ T-cells.  A phase 1 clinical trial is designed to figure out what the right dose is.  Just before they gave me my dose in February the dosage had risen to 450 X 10⁶ T-cells.  Unfortunately, several people had strong adverse reactions to that dose, so they cut the dose back to 150 X 10⁶.  Unfortunately, at least for me, that dose was not enough.  The 4 bags they gave me this time actually amounted to a little more than twice my dose in February, 360 X 10⁶.  So now the question is will this new dose of CAR-T cells do the job?

The reason I am stuck here in the hospital is that some people have a reaction to the CAR-T cells called Cytokine Release Syndrome or CRS.  They take your blood every 4 hours for the first 4 days and every 8 hours thereafter.  They are monitoring 2 components in your blood, CRP and Ferritin.  Both rise precipitously when the body has an intense immune reaction to something.  Cytokines are messenger cells of the immune system that call for other immune cells to come to an infection site.  If too many are released, then parts of your body become inflamed, and bad things can happen to you.  They have treatments for CRS, but you must get them relatively soon after the onset of an attack, so they want you either in the hospital (for the first 14 days) or close to it (for the 16 days after being released from the hospital).

I have been monitoring my CRP and ferritin.  CRP stands for C-reactive Protein, which is produced in the liver and which reacts to inflammatory events.  The normal range for CRP is 0 – 5 and the normal range for ferritin it is 30 to 400.  As you can see, my values are bouncing around in boringly normal levels.

CRP is graphed against the left axis.  They get concerned when it reaches 20.  Ferritin is graphed against the right axis, which doesn’t even get to the top of the normal range.  I don’t know what level causes concern, but I am nowhere close to that.

I sincerely hope that the lack of any reaction is not an indication that nothing is happening.  They tell me there is no correlation between attacks and responses.  In February I never had any attacks, and I did have a response.  It was a partial response, not a complete response, but it was a response.  I am certainly hoping that the new, higher dose will result in a complete response.

I am stuck here in the hospital with little to do.  I do read online newspapers, respond to email, and occasionally watch Senate hearings, but there are lots of hours in the day.  So, I have chosen to take an online course through Yale Online Courses: Philosophy 176, Death.  It was recorded/video taped in 2007.  Professor Shelly Kagan is quite interesting as a lecturer, but that doesn’t mean I can stay awake through an entire 50-minute lecture.  [I had the same problem in History courses when physically at Yale.]  The readings are also interesting, but that doesn’t mean I can stay conscious for more than about 15 pages.  I intersperse walking around, doing other tasks, exercising on a stationary bike, or climbing the stairs.  It is not necessarily the most cheerful of subjects, but the emphasis is on the metaphysics of death, not the physical processes.  People have certainly been speculating and writing about the subject for a long time, so the literature is quite extensive and some of it is interesting.

One of the tasks I have interspersed with my studies is arranging the logistics of staying within 30 minutes of the hospital for the 16 days following my release.  We decided that staying with Brian & Bridget in Jamaica Plain was out this time because they now have 3 mobile boys, 2 of whom are now in school, and likely to be bringing back all sorts of germs from their compatriots.  Instead I will be staying at the Residence Inn Fenway, at Celgene’s expense.  Celgene bought BlueBird Bio, the company what started the clinical trial and was still running it in February.  I also must have a responsible adult monitoring my condition.  Apparently if you get CRS you can temporarily become disabled.  Talking gibberish, losing consciousness, losing your marbles.  The responsible adult needs to realize if such an event is happening and either get me to Beth Israel or call 911 to have the EMTs do it.  Barbie will be the responsible adult Friday noon – Monday noon.  [Do you suppose she is responsible enough?]  For the other 4 days of the week we are hiring a live-in home health aide to be my monitor.

Like last time, I am inviting those who have a museum, event, or institution in Boston that they have been itching to visit to do that visit with me between October 8 and 24.  I hope that those visits and occasional grandchild duty in Jamaica Plain can make the time go by.  So far, so good.  Maybe you get better at this by doing it more than once.  But for me twice is more than enough.

I realize that in February I had expectations that this treatment would be the magic bullet, the cure.  After all, if you have immune cells that can recognize the diseased cells and destroy them, how is the disease going to live on?  Much like immunity to measles, the CAR-T cells should live on.  They will decline in numbers when there are no multiple myeloma cells to attack, but they should retreat to the thalamus (or wherever idle T-cell go) and lay in wait.  Just as the measles immune cells get called whenever a measles virus makes an appearance, so should the CAR-T cells lie in wait for any future multiple myeloma cells to appear.

A report on the BlueBird clinical trial in the June proceedings of the American Society of Clinical Oncology (ASCO) revealed a result that stood out in my mind.  There were many patients who had a positive result, either a partial response such as mine, or a complete result, which means the markers for multiple myeloma went back to the normal range.  The disturbing part of the result is that for those who had a positive response, the disease come back after 11.8 months.  So it buys you a year.  Not a lifetime.  But given the alternatives, I’ll take the 11.8 months and hope I am on the long end of the response range.

I reread the June ASCO report on the bb2121 clinical trial, and it is interesting to observe that what stands out for me depends on what category I think I will be in.  Now that I expect to be in the higher dose category, I expect to have a complete response instead of the partial response I had earlier this year.  Well, it turns out that there is an additional number reported for just those who had a complete response.  The disease did not return until after 17.7 months.  Quite self-centered for me to notice it on this reading and not on the last.  Almost a year and a half.  I’ll take it.

Two Weeks on Hold

I was hoping to be writing this blog post from the hospital while receiving a new (larger) dose of CAR-T cells.  Alas, no, not yet.  My treatment has been postponed for 2 weeks.  Instead of going into Beth Israel on 9/5 for lympho-depleting chemo and receiving the CAR-T cells on 9/10, I hope to do the treatment on 9/19.  It turns out there are complicated rules that govern how you can participate in the clinical trial, and I tripped up on one of them.

For much of the summer I had a growth on my skin at the base of my throat that bothered me.  I called for an appointment at my dermatologist, but the best they could do was give me an appointment 2 months out on August 20^th.  I called a few times to see if I could move it up because of cancellations, but no luck.  They cut it off and sent it for a biopsy.  It turned out to be a squamous cell in situ carcinoma.  To verify that they had removed it completely they scheduled a “scrape and burn” procedure in a week.  I thought that was OK because that was 9/4, just before I was to start the CAR-T treatment. 

But no, it turns out that you are not allowed to start the procedure if you have any open wounds.  The first 3 days they give you lympho-depleting chemo which will reduce your immune system so that the CAR-T cells can more easily take up residence in your body.  But meanwhile you are more open to infection than normal.  Well, should I have started the CAR-Ts first, before dealing with the squamous cells?  No, because you are not allowed to start the treatment if you have any cancerous growth (other than multiple myeloma) bothering you.  So the solution was to have expedited the dermatology appointment in the first place.  Barbie attended the scrape-and-burn session, and she let the dermatologist know her opinion of them not having an appointment for someone with a real problem for 2 months.

The real problem is that life was going to be on hold for the 19 days I was in the hospital.  The net result is that I have nothing going on for the next 2 weeks.  Yes, it is not as boring as sitting in the hospital, but still one's life is on hold.  I just pray that there isn’t something else that comes up to delay the start of the treatment again.  Ideally, the next post will be from the hospital.