An Odd Path for a Magic Bullet

I was surprised to see that my last blog post was just before I was released from the hospital.  Thanks to Celgene's requirement that any study participant spend the first 16 days post hospital release within 30 minutes of the hospital, I’ve had 16 days of hotel living and now 20 days at home since then.  I think of the hospital as prison, the hotel stay as being on parole, and coming home as making bail. 

While close to the hospital, I needed to have a "minder" with me 24/7.  I was fortunate to find Monica, a lady from Trinidad who provides personal care to elderly or infirm people.  She was a good sport as we shared space at the Resident Inn Fenway (great location during the World Series!), and took advantage of many interesting events occurring in Boston.  Barbie became my "minder" from mid-day Fri to mid-day Monday, allowing her to return to Stow for teaching, concert preparation and generally keeping things together at home.  Actually, I wasn’t really in the hotel for the full 16 days.  HUBWeek (a gathering for innovators, entrepreneurs, visionaries, and gadflies sponsored by the Globe, Harvard, MGH, & MIT described here) happened during the first week in the hotel, and I attended a number of sessions there, either with friends or with Monica.  They were quite interesting, and they were quite well attended.  Most of the events were in tents set up at City Hall Plaza, but some were elsewhere in the city.  Generally, I took public transportation to those events, and that may have been my downfall.  Specifically, there was a person sneezing on a Green Line train that was packed, so there was no way to hide.  At any rate the first weekend of my hotel stay / parole, I got a cold.  Scratchy throat on Saturday, followed by more advanced symptoms on Sunday.  I took a nap Sunday afternoon while Barbie studied her Samson scores.  When I woke up, my temperature was 100.6.  My instructions were to report any temperature over 100, which I did.  They said to come into the Emergency Room.  Long story short, they revoked my parole, and I ended up back in prison/hospital through Thursday.

Being confined to the immediate Boston area is not all bad.  I got to see a one-woman play about Black Incarceration.  Barbie, a great fan of getting around by bike rather than car, and I  toured  the Head of the Charles Regatta, which we had never seen, as getting anywhere close by car is impossible.  We saw a film about women kidnapped by Boko Haram, and got to speak with the producer of the film, who had been to Maiduguri (where I was stationed in the Peace Corps).  We saw "Sherlock’s Last Case", a theatrical production at The Huntington Theater.  I was going to visit the Isabella Stewart Gardner Museum with friends, but a Wednesday visit was postponed until the Tuesday after my renewed hospital stay, and it turns out the Gardner is closed on Tuesdays.  So it was off to the Museum of Fine Arts, as there are always exhibits there you never get to.  We think we take good advantage of the many cultural things in Boston, as we live just 25 miles west.  But my experience of semi-captivity in Boston is that we don’t take full advantage of those offerings.

Coming home is like making bail, but I am still under the control of the health care complex.  I have multiple felonies (Multiple Myeloma, a Stem Cell Transplant, and a Whipple) on my record, so I am not totally free and clear, but it is certainly nice to be home.  Just before I was released from the hotel they took 16 vials of blood and did a bone marrow biopsy (BMB).  A BMB involves taking a very large needle and jabbing it into the back of your hip bone, aiming to take a sample of your bone marrow.  That is where the multiple myeloma cells reside and do their dirty work, so the BMB is the ultimate acid test for this disease.  Actually, they take 2 things out of you.  First they take an aspirate of the liquid in the bone marrow.  Then they (try to) take some bone marrow itself.  In my case, the last two times the bone marrow has been too crumply for them to get any bone marrow.  They say the aspirate is good enough, but next time they plan to do the BMB in the Interventional Radiology department so they can better tell exactly where they are.  Apparently my bones have a lot of ridges and they are pretty hard, which makes it difficult.  As you can imagine, in spite of ample numbing, this is not a comfortable procedure!

To date I have primarily discussed the Free Lambda results in this blog, largely because I didn’t understand the BMB results myself.  The reports on the BMB are delayed by 10 days to 3 weeks, so they generally are not very timely.  There are 3 reports, 2 of which are completely incomprehensible.  The third is moderately understandable, but it really has only one number, and I was not always sure of its significance.  So I asked the nurse handling the arrangements for the Clinical Trial, Elisabeth Dwyer, to interpret the latest reports for me.  She went one better, and compiled a history of my BMB results.  Here is a graph she produced:

The discontinuity in the blue line is simply a gap in the data on 2/26/2018.  The orange and gray lines are taken from the analysis of the bone marrow.  That is why they have no data for the last 2 tests.  They also overlay each other on several early tests, as there was no difference between the high and low values.  At any rate, the above graph shows that I was pretty seriously sick in October of 2017.  That was 3 months after my Whipple surgery and during the time when I was blowing through a number of treatments that did not work.  The results were mixed following my receipt of CAR-T Cells on 2/12/18.  Since the higher dose of CAR-T Cells on 9/24, the blue line has been consistently going in the right direction, down.  The readings were 42 on 8/30/18, 29 on 10/9/18, and 25 on 10/22/18.

In contrast, the traditional measure I have been sharing with you in this blog, Free Lambda, has been mixed since my latest dose of CAR-T Cells.  Here is the picture of the last 13 months of Free Lambda, roughly the time corresponding to the BMB graph above:

The last reading before the bigger dose of CAR-T Cells was 685.6 on 9/14/18.  4 weeks after the CAR-Ts, it rose to 776.  A movement of 13% in the wrong direction!  Then on 11/5 it was 654.3, a 16% move in the right direction.  But in fact that is just 5% better than the last reading before the CAR-T cells.  However, I’ll take the better reading and convince myself that it is good news.

The problem is that the two graphs are significantly different.  They both show that I was very sick back in October, 2017.  Then, in spite of the fact that it was deemed that the various treatments I was given in the fall-winter of 2017 had failed, the numbers did come down.  There were far fewer BMB results, so the BMB line is straight, while the Free Lambda line is jagged.  Then in the spring of 2018, the BMB graph gives inconsistent results.  The bone marrow measurements differ from the aspirate numbers.  The Free Lambda graph shows that I got moderately better after the February CAR-Ts, but then progress stopped, and ultimately the disease returned by late August.

Whatever the numbers say, I am feeling really healthy.  I still cannot stand up straight, and I will never run any more road races, but I can putter around the yard or garden and actually get things done.  People tell me I’m looking good, and they have no reason to be buttering me up.

Could this treatment be the magic bullet?  I am allowing myself to hope so.  I have another BMB on the Monday after Thanksgiving, and that should give us more data to evaluate. 

We recently saw Hamilton in Boston, and really enjoyed it.  There are 2 duels in the play.  In each instance, at the point of the shot the action goes into hyper-slow motion, and a dancer shows the path of the bullet with her hands.  It feels as if two different dancers are carrying the message of the state of my Multiple Myeloma via the BMB and Free Lambda numbers.  The fact that the numbers go in different directions a month after the administration of the CAR-T cells may be only a bit of poetic license that the playwright of my life is throwing my way.  Maybe one of the dancers stumbles a bit or the data just has a natural variability.  At any rate, what matters is how I feel, and I am feeling like the bullet has already arrived, and it is MAGIC.

Meanwhile the big event in our lives is Barbie’s concert on the 18^th, which promises to be quite the show.  Handel’s great oratorio "Samson" is a big, complex work that Barbie has been obsessively preparing since the summer.  She has assembled a great batch of soloists, the orchestra is better than ever, and the chorus has been thoroughly taught.  This will be the highlight of the Sounds of Stow’s 40^th year.  Do come if you have any taste for classical music.  The fall concert always kicks off the holiday season for us as it is followed by a big party at our house and a family get together for Thanksgiving.   This year, it will be followed by a two-week trip to Hawaii, where we will be joined by both my sisters.  We both look forward to a get-away following another period of treatment and uncertainty.  But at the moment, things are stable and I am feeling good.  MAGIC.

The view from Feldberg 7

My term as a hospital captive is soon going to come to an end.  Monday, 10/8, I will be partially released - from the security of the hospital, to the luxury and freedom of The Residence Inn at Fenway, a hotel (pretty fancy) that is a 15-minute walk from Beth Israel.  In effect I will be on parole.  Not totally free in that I must have a responsible adult with me 24/7, but on the outside.  I will have many appointments at the hospital (6 in 16 days) and I will be accompanied so that if I should have a CRS event, somebody can get me to the hospital for treatment.  But I will be free to enjoy what is available in Boston.  And there is lots to enjoy.  Including HUBweek (see 2018.hubweek.org), which has lots of events promoting technical innovation or exploring how to plan for the future.

Meanwhile, things here on Feldberg 7 , the floor reserved for hematology/bone marrow transplant patients and where  I have resided many times, things go on in a very predictable pattern.  Every 4 hours they take your vitals (blood pressure, pulse, oxygen %, & temperature), presumably to determine if you are still alive.  I can order food from the room service dining facility, but that gets a bit repetitive.  Or Barbie can bring more interesting food in from outside, especially apples from Honey Pot or soups from a lunch spot she really likes.  A nurse delivers pills and takes blood samples.  I have a PICC line for blood withdrawals, so they don’t have to puncture me each time.  PICC stands for Peripherally Inserted Central Catheter, which is a narrow tube inserted into your upper arm and extending through your veins into a big vein that carries blood to the heart.  They administer medicines, fluids, or nutrition in through the PICC line or take blood out through the PICC line.  Amazingly, the line has not gotten obstructed.  Given how often my feeding tube got obstructed in the summer of 2017 after my Whipple surgery, I am happily surprised that the PICC line has had no trouble like that.  I would have thought that the natural clotting of the blood would have caused blockage.  But they flush the line after each use to keep it clear.  They also say they have a form of draino if it does get blocked, which they have not had to use yet.

There is an extensive care team here at Feldberg 7 at all times.  Feldberg 7 is the Hematology Oncology ward, so everybody here has some form of cancer that affects the blood or blood system.  Leukemia, lymphoma, myeloma, etc.  There are lots of ways the blood system can go wrong, and lots of ways they can fight it.  As I have done the surface research into my own disease I have come to think that maybe it is more amazing that the normal blood system works correctly, it is so complicated.  The care team consists of (in descending order of status) doctors, physician’s assistants, nurses, physical care assistants, and cleaning staff.  These were my care givers on Friday, 10/5.

Carlota, my PCT (Personal Care Technician).

Julie, my nurse.  The document in her hand is the order that accompanies the blood vials she has just extracted on their journey to the blood testing lab or the company running the clinical trial, now Celgene.

Ijeoma, my Physician’s Assistant.  She was born in the US to Nigerian parents who were studying here.  She was raised in the Eastern Region of Nigeria, and then returned to the US for her studies.  She has recently completed her dissertation for a PHD, so she is quite accomplished.  We have had quite extensive discussions about where each of us have lived in Nigeria, what we experienced there, and what needs to happen to make Nigeria work better as a country and a society.  We haven’t come up with any magic bullets in our conversations, yet.

This is the full medical team.  Dr. Nahas to the left, is my oncologist.  Ijeoma in the middle, and Julie to the right.  As you can see, I have lots of women taking care of me.  There is the occasional male doctor, nurse, or pct, but they are a very small minority.  

All day, every day, the nurses check on you and do medicines and bloods.  Julie was the nurse who administered the CAR-T Cells on Day 0 of this process.  Every day about mid-morning the PA comes around, asking if I have any new symptoms, listening to my lungs and heart, ready to recommend any changes in treatment.  But I always have disappointed them during this stay, as I have had no adverse reactions.  Later in the morning the complete medical team does “rounds”.  The doctor, PA, & nurse arrive for an official visit.  The doctor performs another listen and general evaluation, while the nurse and PA provide any observations they have made in the last 24 hours.  Since nothing externally visible is happening, these rounds are short and sweet.  I recall when I was in for the Whipple, the team on rounds consisted of many doctors, residents, and interns, in addition to the PA and nurse.  Presumably that was because I was a much more interesting subject, as I was recovering from 9 hours of surgery.

The markers they track to assess a possible CRS (cytokine release syndrome) event are still doing nothing.They have reduced the blood testing to once a day, so it is not so bothersome.

Barbie comes in on weekends and Brian, Brendan, and Jack have come in for visits.  The grandchildren exhibit a level of vitality that simply is not seen on the hospital floor.  The visits actually occur in a family room just outside the official confines of the Hematology/Oncology ward, as children under 12 are not allowed into the ward.  They are far too dangerous as sources of infection to be allowed into the ward.  Many patients in the ward have immune systems that are seriously compromised, and exposure to germ factories of 5 and 3 years old could be disastrous.  Generally, we have a full schedule of eating something, reading a kid’s book, and playing with sterile gloves.  The gloves get inflated to be a cross between a balloon and an udder, and then bounced up into the air and fought over.

Eventually they do pop and leave shreds all over the floor.  It turns out that normal balloons, with their narrow necks, are much better designed than gloves for tying off.  It is really hard to gather the wrist of the glove and effectively tie it, so it holds air.  Could it be that these gloves were not designed to be used as balloons?

I am looking forward to my release tomorrow.  Then it is onto a new stage of this adventure.  They have not chosen to do any tests of my free lambda, the normal test for the level of my multiple myeloma.  The reason advanced is that the free lambda is a slowly reacting marker.  It does not react immediately to changes in the underlying level of the disease.  It is a lagging indicator, so there is no point in testing it too early.  I believe they will test in on my final day, so we will then get an indication of what has happened.  Needless to say, my fingers are crossed.  The ultimate test is the bone marrow biopsy.  Since tomorrow is Columbus Day and since Barbie needs to get back to Stow for piano lessons and a chorus rehearsal, the bone marrow biopsy will be done on Tuesday morning.  It shows what is happening in the bone marrow itself, so there is no lag.  But the reports of the bone marrow biopsy take 10 days to 2 weeks to come back, so there is a lag built into them a well.  Either way it is hard to get a good reading on what is happening with the disease.  It is easy to tell yourself to be patient, but difficult to sit and wait for the results.

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.

Time for a Re-do

Friday Barbie & I met with my oncology team.  Usually such meetings are somewhat hypothetical, as the key test, Free Lambda, takes 36-48 hours to come back.  Knowing that, I had driven down to Beth Israel on Wednesday and had them take my blood early, so that the Free Lambda would be known.  Actually, the results came back in less than 24 hours: 461.9 (new scale), which is 660.5 on the old scale.  Since 500+ on the old scale was considered Multiple Myeloma at full rage, 660 is more than enough.

The reason Barbie attended the meeting was to plead for a re-administration of the CAR-T Cell therapy at the newly recommended level.  But I got a call from Elizabeth Dwyer, the nurse administering the clinical trial, on Thursday informing me that my new Free Lambda reading qualified me for the re-do.  They took blood for another Free Lambda test on Friday, just to confirm that the reading was not a fluke.  So, the discussion on Friday was largely about the details of when to have the repeat treatment at the higher dose level. 

The issue of the dosage was a result of a judgement by the company running the clinical trial, Blue Bird Bio.  They had gradually increased the dose as the trial went on, reaching a level of 450 X 10⁶ cells just before I entered the trial.  Unfortunately, there was a severe reaction to the 450 dose, so they fell back to 150 X 10⁶ cells.  That was the dose they gave me.  Unfortunately, that dose turned out to be only partially effective.  There were patients who had a complete response at that level, but there were more who had just a partial response.  I was one of the partial response patients.  Yes, my Free Lambda came down, but then it went sideways.  It never reached a “normal” level.  They have since decided that 300 X 10⁶ cells is the correct dose.  That is what I will get when they administer the re-do.

Elizabeth Dwyer communicated with Blue Bird Bio, now Celgene Corporation.  They do have enough of my CAR-T Cells to give me a 300 X 10⁶ cells dose.  It would just take them 3 days to ship them to Beth Israel.  I could start as soon as next week.  But next week I have a Friends of Nigeria meeting in Delaware Water Gap, PA.  Then the following week we have family coming to New Hampshire, so we asked to delay the re-do until after Labor Day.  The team thought that would be OK.

A re-do involves just the same process that I went through last February.  3 days of lymphodepletion chemotherapy, followed by a weekend to recover.  Then the infusion of the CAR-T Cells on a Monday, followed by 2 days of monitoring every 4 hours.  Gradually the monitoring frequency is reduced until some of the tests are done just once a day.  One has the privilege of staying in the hospital for 14 days after receiving the CAR-T Cells, a form of torture by inactivity.  Then for another 14 days you are supposed to stay within 30 minutes of the hospital and have someone monitoring you all the time.  For me that means staying with Brian & Bridget in Jamaica Plain.  It is great to spend time with the grandkids, but it is an imposition on their family, and it further postpones getting back to real life.

Barbie & I had all sorts of questions.  There was a major report on the clinical trial at the ASCO (American Society of Clinical Oncology) Annual Meeting in Chicago in June.  One thing I noticed was that while there was a high rate of Complete Responses (CR) for those who got the higher dose, CR did not mean the disease was gone.  Instead, the mean time before the return of the disease was 11.8 months.  They refer to this as PFS – progression free survival.  Which means the treatment can get you back down to the normal range for whatever is your measure of the disease, but you may or may not stay there.  So, it has good results, but it is not the magic bullet we were counting on.  Dr. Nahas did say that they have found that after the CAR-T Cell treatment other drugs that formerly had ceased having any effect, often become effective again. 

We asked how the disease would return, given our understanding of how the CAR-T Cells work.  There was lots of speculation, but it came down to the fact that there are very few people who have been through the treatment.  The clinical trial has been expanded to include 65 people, but statistically 65 is a very small number.  And there are many different types of Multiple Myeloma and many different types of patients.  The conclusion was that it is still early days, and we have yet to learn some of the crucial answers.

The ASCO report is a good source of acronyms.  One that I like is RRMM.  It stands for Relapsed/Refractory Multiple Myeloma, which is required to qualify for the clinical trial.  Barbie suggests that just as some people put their academic or professional qualifications after their name (ESQ, PHD, FAGD), I should put my disease classification behind my name: Gregory Jones, RRMM.  Sounds distinguished.  Another way of saying a 3-time loser.

Meanwhile RRMM continues to make its presence in my body known.  I get out of breath with relatively little exercise.  Dr. Nahas noticed that my blood is iron-deficient, which would result in less oxygen being delivered by the blood, so I am scheduled for an iron infusion on Tuesday.  I complained of something in my right lower abdomen, just along the fold where your tummy and leg join.  As a result, they will perform a PET-scan, which images your entire body.  It really feels as if something is in there, but what do I know?

We are very happy that I qualify for a re-treatment.  But it becomes clear that our hopes for the treatment were overly optimistic.  Yes, it is a good treatment, but no, it is not a magic bullet.

Good News, Bad News

I haven’t posted since 4/13/18, as I have been waiting for a resolution to what is happening with me.  Since that is unlikely to happen any time soon, I will attempt to describe the current situation with all its uncertainties. 

If you consult the graph of free lambda readings following the infusion of “weaponized” CAR-T cells on February 12th, what originally appeared as a jagged lightning bolt going down turned into a hockey stick in April. Through April and most of May, things went sideways.  Slightly up, but not drastically so.  It was as if the CAR-T cells were resting. 

Then at the end of May there was a dramatic uptick.  Free Lambda went from 465 to 552, an increase of 87 or 19%.  This indicated the disease was progressing.  The person who monitors clinical trials at Beth Israel contacted the people at Bluebird Bio, to see if they had enough of my weaponized T-cells for another dose.  The answer was yes, and the recommended dose was 3 million cells.  That revealed something I had not realized before.  I had assumed that since I was relatively late in the clinical trial that the optimum dose had already been worked out.  Not so.  They had gradually increased the dose during the clinical trial to 4.5 million cells.  At that level several of the patients had severe reactions to the treatment.  So they scaled back the dose to 1.5 million cells, which is what they gave me.  It would appear that 1.5 million is not enough, and if I were to get a new treatment, the dose would be 3 million cells.  Maybe that explains why my free lambda went sideways during April + May and shot up at the end of May.  Maybe.

Actually, the dosage issue was a bit of a relief.  I had not realized how much I was counting on this treatment being the magic bullet to cure my multiple myeloma.  But how could it be a magic bullet if the disease was still acting up?  Did I have myeloma cells that did not express the protein the T-cells were primed to look for?  Did some of the blood samples that the clinical trial required to be collected every month have information that would explain the continued activity of the disease?  I asked these questions of my doctors and the clinical trial person, but apparently the scientists at the company running the clinical trial don’t release information to the local doctors until periodic times later in the trial.

However, they don’t act on a single reading, because of the variability of the tests.  So, the following Friday I had another free lambda test.  We were planning to attend a niece’s wedding in Florida 2 weeks after that, but if need be, I was willing to skip the wedding to get the re-treatment.  Clearly I was hoping for another bad reading.  So, naturally, the reading was good.  A new low since a year ago: 421.6.  Since the reading indicated the multiple myeloma was not progressing, I did not qualify to receive a new batch of CAR-T cells.  So the good news was also bad news.

What a bummer! 

But 421.6 is actually good news, so how do we deal with that?  Does it mean the CAR-T cells have suddenly come back to life?  Was there some combination of side infection or other things going on in my body that hampered the action so the CAR-T cells?  We don’t know, but better is still good. 

Then, just to prove how perverse this all can be, I had another reading this past Monday.  Back up to 511.2.  The wrong direction again.  Sigh.  Here is the overall picture of the last 15 months:

So I won’t be getting a re-treatment of the CAR-T cells anytime soon.  I asked if the latest reading confirmed the uptick to 552.  No, it does not.  But the good news is that I won’t have to sacrifice a month of my summer to being in the hospital or close to it receiving the cells.  So the last interaction with the oncologist this past Monday was, “See you in a month, but if anything happens in the meantime, be sure to get in touch with us.” 

But wait.  Early Wednesday morning I awoke with a painful stomach ache.  I got up and took some pain killers, but they didn’t really have much effect.  In the morning I got up and took my pills, but I still felt rotten, and in very low gear.  45 minutes after taking my pills, I threw up.  So I called the medical teams, both the multiple myeloma team and the surgery team that did the Whipple surgery a year ago.  They both said to come into the hospital.  I went into the multiple myeloma team.  They took some blood, listened, and poked around, but had no idea.  They sent me for a CT scan of my abdomen and administered some IV fluids because I hadn’t drunk any liquids all day.  They were about to release me to go to my son’s house in Jamaica Plain when the results from the CT scan came back: an obstruction in the small intestine causing a major backup in the intestine above the blockage.  The first time in a long time that a diagnostic test actually provided a clear answer!  So it was off the ER while they figured out where and how to admit me.  Just as the ambulance people arrived to move me to the West Campus of Beth Israel, I threw up a second time.  Both eruptions were quite large, very liquid, and pretty clearly stuff that was in the midst of being digested.  I felt MUCH better after throwing up.  And throwing up was good in that it relieved the pressure on the obstruction, making it easier for it to resolve itself.  Early the next morning after being admitted to a room that was in the surgical domain, I had a bowel movement that apparently was the blockage ‘passing’.  Problem solved, all within 24 hours.  But convincing the doctors that I was OK and could be released took until 2:30, but I was able to make a local 5PM meeting here in Stow.  Just a small amount of drama.  So we can now resume our normal programming, worrying about the next step in my multiple myeloma saga.

Predictable and inevitable complications of the Whipple surgery, performed exactly one year ago today, piggy-backing on the multiple myeloma make for continued roller coaster rides and unpredictable trips to the hospital.  Barbie finds it very difficult to make definite plans for anything, and we have continued to rely on Brian and Bridget’s hospitality.  Multiple friends have also helped in driving to and from Boston.  “It takes a village to raise a child” can just as easily apply to the process of helping someone through the vagaries and demands of a major illness (or two).

Stay tuned….

An Emotional Rollercoaster

Recently I have gotten very different Free Lambda readings.  Since I was released from the hospital they have taken Free Lambda tests weekly.  When the readings are positive (lower), I feel great.  When they are negative (higher) not so great.  I find it useful to graph the results, as a picture tells me more.  So when the graph looks like this:

And the right end of the graph is decidedly DOWN, I feel great.  This was accompanied by a Bone Marrow Biopsy (BMB) with a reading of 30%.  That means 30% of a particular type of cell in the bone marrow is affected by Multiple Myeloma.  I have access to the BMB reports through the patient portal at Beth Israel, but they are gibberish to me.  But again, a lower number is better.  The clinical trial requires BMBs, as there are several different flavors of Multiple Myeloma, and they don’t all result in elevated levels of Free Lambda.

But the very next week, the results were not so good:

Not only is the graph now going up, it was accompanied by a BMB where the result was 50%.  The doctor said not to panic, but it is hard not to.  She explained that the higher % could be the result of finding fewer of the cells they were looking for in the sample from the interior of my bone.  As I explained it to Barbie, if the first BMB found 10 cells and 3 of them were Multiple Myeloma cells, that would be 30%.  But if the second test only found 6 cells, then 3 Multiple Myeloma cells would be 50%.  All that makes a certain amount of sense, but I was very aware that I was straining reality to put a positive spin on things.

So the next week had a very different result:

Here we are again, going down very positively.  In fact, when you look at the graph over the entire time I’ve had MM, the end looks even more dramatic:

The right hand tail of the graph is really going down.  I felt great!  In fact by isolating the last part of the graph, it looks like a lightning bolt:

Naturally, this last Friday the results were not so positive.  Again, the Free Lambda went up slightly.  The doctors explain that the tests are not exact.  There is sampling error, statistical error, measuring error.  So we should not look at any reading as an exact number.  Instead it is within a sampling error of the actual value.  So the thing to look at is the long term trend.  Again, as a patient, I can hear them telling me to be patient, not to hit the panic button.  But it happens anyway.

When you take the end of the full range graph, what was a lightning bolt is now a bit of a hockey stick:

It is still better than if it went up significantly, and it clearly must be within a statistical error of a good reading, but it is still going in the wrong direction.

Generally, except for my back, I am feeling good.  As I sit here at my computer, I feel fine.  But if I stand for a long while, my back gets tired fast.  I discovered that using a walker at the Museum of Fine Arts in Boston relieved my back of much of the stress of my weight hunched forward.  I plan to use the walker (assuming it is OK for outdoor use) in the Multiple Myeloma Research Foundation 5K race/walk on April 29^th.  I have appealed to the usual range of suspects, and you friends and family have come through in a very generous way.  We already have a team of 11, but if you are available and inspired, you can certainly join us.  The team has already raised $6,030, and I have not yet finished hounding my contact list.  I feel incredibly grateful that I have benefited from the results of modern medical research.  30 years ago, it would have been 2 years and out.  If the CAR-T cell therapy works as advertised, I should end up with “no observable disease”.  Thank you Modern Medicine.

A Free Man

My last post was from the hospital on 2/21, when the tedium of the hospital was overwhelming.  I did get out on 2/26, and I spent the next 16 days with my son & daughter-in-law in Jamaica Plain.  They have 3 boys, ages 5, 3, & 6 months, so life there was rarely boring.  Generally the boys were always interested in having stories read to them, fighting with each other, running the track that connects their living room, dining room, kitchen, & front hallway, and torturing their parents.  I also became a surprisingly bad player of Connect-4.  To avoid interfering with the daily activities of their nanny, I endeavored to get out during the week and use my presence in JP as an excuse to visit Boston cultural icons I had never (or not recently) visited.  I had to be accompanied by a responsible adult, as who knew when a nasty side effect of the CAR-T cells would strike me.  I managed to visit the New England Aquarium, the Harvard Museum of Natural History, the ICA, and the MIT Museum before a combination of a bad cold and a major snowstorm shut the Boston cultural tour down.  The MFA and the Isabella Stuart Gardner Museum were next on the calendar, but I’ll have to drive in from Stow to take them in.  My actual and would-be companions (Sandy, Dave, Scott, Paul, Myle, Kate, & John) were not always recognizable as responsible adults, but I appreciate their being willing to put up with my company.

I have been a home-dweller, not a guest imposing, since Wednesday.  It is great to be on home turf.  In spite of wonderful hospitality and very entertaining grandchildren in Jamaica Plain, there is no place like home, to coin a phrase.

Originally I was going to have the 30-day bone marrow biopsy (bmb) on Wednesday, which was rescheduled from Friday due to a doctor conflict.  But they neglected to tell me not to take my lovenox shot Wednesday morning, and I dutifully jabbed myself, in spite of hating the process.  Apparently a bmb is incompatible with lovenox, so the bmb had to be postponed.  But they did take all sorts of blood tests on Wednesday, so they only had to take a few on Friday.

The bmb is quite an elaborate procedure.  They have you lie face down on an examination table.  Lying face down is difficult for me, as the curvature of my back means it takes me quite a while to flatten out.  Doing so while lying on my back actually feels quite nice, as the tightness of my chest gets relieved, and it feels quite good.  But lying face down does not feel so good, and the result is that you can only see the people on the side where your face is turned.  They pick out the part of the hip they are going to aim for, and mark it with a magic marker.  Then they surgically clean the area and drape it with sterile dressings.  Then they shoot a number of pain killers in the immediate area, to completely numb the surface.  The shots themselves hurt a bit, but presumably they are preventing much greater pain.  They ask periodically if you are feeling any pain, and generally the answer is NO.  But just think, the Civil War was not that long ago, and they did amputations without any anesthesia.  We have come a long way.  Eventually they start to excavate and penetrate.  It doesn’t hurt, but there is enough pressure back there that it feels like it should.  Clearly something invasive is going on, and it takes just about all the doctor’s strength to penetrate the bone.  They go in several times, first pulling out actual bone marrow, then pulling out an aspirate, or liquid from the bone interior.

About half way through the process, Doctor Nahas remarked that my Free Lambda reading on Wednesday was a big improvement.  I hadn’t checked the BIDMC Patient Site to find Wednesday’s result.  570.4!  Down from 875!  That means the CAR-T cells are working.  That is a 35% reduction.  Still a long way to go (normal max is 26), but strong movement in the right direction.  Here is the graph of the last 18 months of Free Lambda:

Suddenly, all the pulling and tugging in my back/backside was irrelevant.  Anyway, they don’t get the results of a bmb back until at least a week out, which makes the Free Lambda test seem lightning quick in comparison.  Last time we had to try to convince ourselves that a near unchanged Free Lambda reading was actually good because it wasn’t getting any worse.  Such a rose-colored-glasses interpretation is no longer necessary.  Things are really getting better, to a significant degree.

I came home to my normal computer, my normal bed, a kitchen where I’ve known the rules for a long time.  I had 1800 emails to wade through.  As of today I am all caught up.  I am back to current state as Treasurer of the Stow Community Housing Corp, which owns and runs 140 affordable apartments in Stow.  The last 2 snow storms have resulted in a great deal of tree damage in our yard, and we had a crew come with a bucket crane to cut out all the broken branches.  Then they ground all the branches they could get to into wood chips.  The place looks much better, but once the snow is gone there will be a massive cleanup required.  Then just today people came to fill in the trench across the driveway cut to lay the cable from the barn to the house for the solar panels.  They cut the trench back in December, but cold weather and then snow foiled all the dates set for filling in and finishing off the trench.  In other words, life is getting back to normal.

Until the positive reading on the Free Lambda, my planning horizon was at most a month.  At first the hospital stay and the JP stay dictated what I would be doing.  Now that we can see that things are really getting better, perhaps we can look a little further out.  I have decided once again to organize the Greg’s Legs team to participate in the Boston MMRF 5K Run/Walk on 4/29.  So everybody should expect a recruiting / donation begging email in the near future.  If you don’t drop me an email, and I’ll add you to the dunning list.  I will contact the back doctor to see if anything can be done to straighten out and lengthen my back.  We spoke with him back toward the end of January, but he said as long as the effects of Multiple Myeloma are still being felt, making repairs to individual vertebrae would only result in neighboring vertebrae breaking.  The timing of when this should take place is probably a function of how fast the Multiple Myeloma recedes.

My overwhelming emotion is gratitude.  Thankfulness that I have been lucky enough to participate in the CAR-T cell clinical trial.  Hopeful that my improvement continues to the point where I reach the state of “no observable disease” which so many other participants in these clinical trials have achieved.  To see the results of this clinical trial as announced at the American Society of Hematology annual meeting in December see www.epgonline.org/us/news/results-from-phase-i-trial-of-bb-2121--a-car-t-cell-therapy--for-multiple-myeloma---celgene---bluebird-bio.  This data was released just about the time I was being enrolled in the trial, so it does not include me.  And many of the participants at that time had not been in the trial long enough to have any results.  But clearly the results were very positive for those in the trial for an extended time period, and there is no reason I should not see the same results in time.  Again, gratitude.  Wow, have I been lucky!