The Wrong Direction

I just reviewed my blog post of September 13.  I wrote about a Free Lambda reading of 2752 being a new record.  Well a reading of 4879 on 9/24 sure put that to shame.  Luckily, the next reading on 10/1 was 2076 lower at 2803.  That gave an indication that the Elotuzumab was finally kicking in and having an effect.  But the latest on 10/15 was 2970, an increase of 167 and going in the wrong direction.  I wonder if the Elotuzumab has lost its effectiveness.

Here is the latest graph of the last year:

Whereas in the spring 2 doses of Elotuzumab brought the Free Lambda right down, the latest behavior is not so promising.  The big spike to 4879 happened after 3 doses of Elotuzumab.  Then it came back down dramatically, but it has just gone up to what would once have been a record.  I wonder if the 5 doses of Elotuzumab in the spring gave my Multiple Myeloma enough exposure to Elotuzumab to figure out a way around it.

Two and a half weeks ago, in spite of the high numbers I was feeling very good.  I took a brisk walk in the neighborhood using my walker, and I actually felt as if I was power-walking.  So I went out back and attacked some vines that overgrow the cedar trees in our pasture.  Well I overdid it trying to uproot the vines, and I think I broke a high rib or bruised my sternum.  At any rate, ever since my chest has been hurting.  I have been taking pain killers, but coughing or sneezing really exacerbates the pain.  My upper back is very bent so I can no longer do exercises on a mat on the floor, as my upper back hurts and does not straighten out.  A certain wife points out that I have nobody to blame except myself for this.  Sigh.

I did ask Dr. Nahas recently if 4800 is an unusually high reading.  She said she has seen readings of 30 – 40,000, but by that time you are in the hospital on dialysis because otherwise the Free Lambda would overwhelm your kidneys.  So where I am now is concerning, but not an emergency.  My next appointment is this coming Tuesday, and I wonder what the tactical response will be.  More to come soon, but I thought I’d keep you up to date on what has just happened.

Unchartered Territory

First some good news.  My left hip is pretty well healed.  I met with the surgeon on Tuesday, and he says it is looking good.  I commented that the outside of my hip hurts when I lie on my left side.  Dr. Wixted pulled up an X-ray of my hip, and showed how there is a metal fixture holding the screw that extends into the head of the femur.  The screw’s job is to stabilize the head and pull the broken parts together.  As the bone heals, the length of the neck gets shorter.  The metal fixture is anchored in a metal brace that goes the vertical length of the femur.  The fixture must have some sort of ratchet mechanism, because as the neck gets shorter, the fixture backs out of the brace.  There is now about a half inch of the fixture sticking out of the outside of the brace.  That is what I am feeling.  They can replace the fixture with a shorter one, but they would not do anything until a year out.

I also commented that the left hip joint does not flex as far as the right one.  Dr. Wixted said that was also due to the shortening of the neck of the femur.  The head of the femur is the ball of a ball-and-socket joint.  The shoulder of the femur gets closer to the head as the neck shortens.  When I try to bend the hip fully, the shoulder of the femur bumps into the hip bone, limiting the range of motion.  I should still do stretching exercises to maximize the range of motion, but I should not expect to achieve the pre-surgery range.

It is now 4+ months since I broke the hip and had the surgery.  Things are going well.

I wish I could say the same on the multiple myeloma front.  At the end of May, I entered a clinical trial for a multiple myeloma vaccine.  Unfortunately, the vaccine has not worked for me.  For unknown reasons, they did not test for free lambda during the month of August.  When I had the 5^th round of bi-weekly vaccine treatments on September 3^rd, my free lambda was 1,952, an alarmingly high value, up from 716 on July 23rd   They had me come in again to retest it, which confirmed that the reading was accurate.  So on 9/10 they put me back on the treatment that proved to be effective in the spring, a combination of Elotuzumab and Velcade.  Although this combination reduced the free lambda number quickly, they suspended these drugs when I fell and broke my hip. Then they tried the vaccine – which hasn’t worked.

Prior to Tuesday’s Elotuzumab/Velcade treatment, they took another reading of free lambda, and we are at a new high – unchartered territory.  Here is a graph of recent values:

The prior high was 2,604 on April 11.  At 2,752 we have a new record!  This is more than 100 times the max of the normal range.  I am sure hoping the Elotuzumab does its magic again.  The concern is that multiple myeloma is pretty good at evolving around treatments.  When I was on the clinical trial for CAR-T cells, I got an inadequate dose to start.  Then later they gave me what was then understood to be the recommended dose.  But my multiple myeloma simply shrugged off the fuller dose, and proceeded to assert itself.  We sure hope a similar pattern does not appear here.

During the spring when my free lambda was high, I was pretty sick and spent several sessions in the hospital.  The good news is that I am feeling relatively well, in spite of the numbers.  I am bent over more than before, but I don’t think that is the result of any new compression fractures.  I have progressed from favoring my hip.  Now when I try to do chores without any external form of support, my back gets tired very quickly.  Once it gets really tired, it hurts.  So when I go for a walk, I use my rollator.  And I limit the time I do unsupported activities.  Even standing around socializing gets tiring, and I find myself seeking out a chair (which tends to limit social interaction).

A big question is whether we will be able to go on a trip Barbie has planned to Prince Edward Island.  The idea is to leave on Wednesday, 9/18, and return Sunday, 9/29.  That was timed to correspond to the gap between the 6^th and 7^th bi-weekly applications of the vaccine clinical trial.  Now I am on a completely different treatment plan, and the trip may or may not interfere with the treatment.  The documentation they had me give the nurse on Tuesday called for a second treatment on 9/24, which would be right in the middle of our trip.  I just spoke with the research nurse, and she said the normal course of Elotuzumab treatments is weekly to start, and then bi-weekly.  Because I had gotten Elotuzumab back in the spring, the idea was to jump right to the biweekly treatments.  But the distressingly high free lambda will probably indicate a weekly treatment on 9/17, and then a 2-week interval.  The doctors are aware of our travel plans, and they have said they will plan around them.  But medical events have a way of taking precedence over the best laid plans.

Healing + New Clinical Trial

Since my last blog post, both Barbie & I have been healing, undergoing physical therapy (me) or occupational therapy (Barbie).  Except for occasional setbacks when the body part involved gets banged or abused in some way, the progress has been encouraging.  In spite of stubbornly resistant tendons, Barbie is slowly regaining some flexibility in her wrist, and I have evolved from dependence on two crutches, to a single crutch, then a cane, and recently walking short distances without any extra support. My “Cadillac” rollator helps me accomplish longer walks, if smooth surfaces are available.

The other main development since May 30^th is that I have started a new clinical trial of a vaccine for Multiple Myeloma.  Through the spring it was nip and tuck whether I would qualify for the clinical trial.  The interim medicine was working too well, so I was not “sick” enough to qualify.  My fall and broken hip resulted in my skipping a treatment, causing in an increase in my free lambda, which qualified me for the clinical trial.  Another irony is that while I was ill, in a conventional sense, basically from Feb. until the hip-breaking fall, the large doses of meds administered while they were addressing the hip fracture seemed to clear up whatever had been plaguing me.  So breaking my hip resulted in my getting “better” as well as allowing me to qualify to participate in the new vaccine trial.  I am patient #001.

They make the vaccine by taking your multiple myeloma cells via a bone marrow biopsy.  In my case they had to do 2 bone marrow biopsies because the first time they didn’t get the requisite number of cells.  The goal was 10 million cells, and they only got 7.5 million on the first try.  Usually getting that number of cells is easy, as 10 million cells amounts to a very small layer in a test tube.  But they didn’t get the needed amount, so they drilled into my hip bone again.  Lucky me.

Once they had the right number of myeloma cells, they extracted dendridic white blood cells.  This required them hooking me up to a blood centrifuge.  One line in a vein in my right arm fed fresh blood into the machine, and then the “used” blood was returned to another line in my left arm.  Very large bore needles are needed to capture the required volume of blood flow, and the IVs were somewhat temperamental, requiring frequent adjustments.  While this was happening, I got a call from Barbie calling from the ER in Concord, MA announcing that she had broken her wrist.  Suddenly what I was doing seemed less critical.

It took about a month for them to create the vaccine.  The actual clinical trial consists of 12 infusions of Nivolumab, every 2 weeks.  Nivolumab is a monoclonal antibody that acts to prevent the cancer's mechanism that turns off the immune system's T-cells from working.  It is not frequently used for Multiple Myeloma patients, hence the trial.  Then on infusions #1, #3, & #5 I also get a shot of the vaccine followed by booster shots of GM-CSF on that day and the next 3 days.  GM-CSF stands for Granulocyte macrophage colony-stimulating factor.  I have read the Wikipedia entry for GM-CSF as well as several other internet articles on GM-CSF.  Suffice it to say the explanations are way more technical than I can understand.  Net: GM-CSF is supposed to enhance the effect of the vaccine.

The clinical trial has a long document that the patient must sign in multiple places.  It lists the possible side effects of each of the components of the clinical trial.  Many of the side effects are said to happen in more than 50% of the patients.  So far, I have only had one side effect: an itchy rash in the area of the vaccine injection and the GM-CSF injections.  I have no idea whether it is from the vaccine or the GM-CSF.  Luckily if I don’t scratch it, it gets no worse.

So far it is not clear that the vaccine has had any significant effect.  My latest free lambda is 716, up from 630 a month earlier.  It is going in the wrong direction, but not significantly so.  It is always hard to tell what would have happened in the absence of the current treatment.  Would it have spiked up like it did in the spring?  They have certainly taken lots of blood tests as part of the clinical trial.  Maybe one of them can tell us what is going on.

This summer we are splitting our time between Cow Island and Stow.  We have physical/occupational therapy both in New Hampshire and at home.  My clinical trial appointments dictate when we are in Stow.  Generally, we spend 10 days in New Hampshire and 4 days in Stow.  The New Hampshire PT/OT is in Guilford, which is on the southern side of Lake Winnipesaukee.  Sometimes we have arranged to leave from there going back to Stow, as it cuts 45 minutes off the trip. 

One of the joys of our NH island camp is the ability to stay off the roads, to stay put and enjoy living closer to our beautiful natural setting and avoid driving, traffic and other hassles.  This summer, with far more frequent trips to and from MA and hauling ourselves to PT/OT twice a week, we have not had the uninterrupted quiet time up here.  But we are grateful to have found good therapy services in both places, and so far, we have been able to negotiate the more challenging aspects of being on the island on our own – thanks to the help of our sons and their families who did so much of the heavy lifting required to set the place up over the July 4 weekend. We are also very fortunate to have a wonderful carpenter/handyman who has helped with things that we cannot manage ourselves in our compromised states.  So we will enjoy this summer as much as we can, though we miss our sailboat and all the enjoyment it has given us over the years. Hopefully next summer we will both be fit enough to handle it and we can get back to “normal.” Stay tuned….

An Accident-prone Family

I spent 5/11 – 5/25 in Life Care Center of Nashoba Valley, a rehab facility in Littleton, 15 minutes away from our home here in Stow.  They take physical and occupational therapy very seriously there, and I was able to make good progress in recovering my ability to walk and maneuver.  I had a number of appointments in at Beth Israel that advanced the cause of my participating in a clinical trial of a Multiple Myeloma vaccine.  All looked fine for a normal release to home and Barbie’s care.

Then Thursday, 5/23, Barbie fell on the tennis court and severely broke her left wrist. 

EMTs brought her to Emerson Hospital in Concord Massachusetts where she received excellent and timely care from skilled ER doctors. They performed a process known as reduction, where the hand is suspended from the fingers while someone gently massages the bones back into proper alignment. A solid cast is affixed to preserve the alignment until surgery. This was done while Barbie was receiving quantities of pain medicines which managed to affect the entire body except the incredibly painful wrist!  A dissociative drug, ketamine, provided her with the first truly hallucinogenic trip of her life. Son Brian was there to help interface with doctors at Emerson and those his wife Bridget was lining up to perform surgery in Boston the following day. 

Turns out Barbie managed to break both her radius and ulna as well as some of the smaller bones in the wrist 

so it is a pretty complex fracture of an important part of the body for anyone, even more so for someone who 

loves to play the piano! Brian took her from Emerson to his home in Boston, then delivered her for surgery 

Friday morning. Apparently, the surgery went well, but Barbie was still asleep when the surgeon came by to 

deliver the post-surgery report.  Needless to say, Barbie was in major pain and the pain killers struggled to keep 

up with the intensity.

Saturday Andrew and Gabriel (age 4) drove down from Vermont to Jamaica Plain to pick Barbie up.  Brian’s son Brendan (age 6) came along as a playmate for Gabriel.  Then they drove to Littleton to pick me up, who was being discharged into what was intended to be a stable home environment.  Barbie was pretty well incapacitated, but Andrew provided all the care and feeding required for both of us.  In addition, he did a number of chores around the house that had piled up in my absence, such as putting in screens and getting the tractor into summer use shape.  Brendan and Gabriel had a great time playing in the yard with bikes and various toys from our barn.

Sunday Andrew made breakfast and brush hogged the pasture.  Then he and Gabriel headed back to Vermont while Brian came out from Jamaica Plain with Jack (age 4).  By Sunday Barbie was feeling better as the distortions of the systemic pain killers were wearing off.  Now the problem is swelling.  

The instructions are to keep the wrist above the heart to minimize the swelling.  Barbie has been sleeping on the couch, as that enables her to keep the wrist well elevated all night long.  Still, the swelling remains a problem.  We had a visiting nurse come Tuesday to evaluate our home situation and arrange for various home therapies.  She agreed with Barbie that the swelling was worrisome, and Barbie has been in touch with the surgeon’s office to see if this is “normal”.

Meanwhile our local caring network at First Parish Church has leapt into action as well.  We have meals every other day through June 21^st.  People appear to be competing for cooking kudos, as each recipe sounds more enticing than the last.  We also have rides to our various appointments, as neither of us can drive just now.  We also have many willing and helpful hands in the chorus and among the piano parents, for which we are very grateful.

Who could have dreamed up this plot twist?  Barbie likes to say she was tired of me getting all the attention, but this is a rather extreme way to grab the spotlight.  At this point we are doing fairly well on our own, as Barbie provides the legs for moving things around and I provide the hands to open jars and packages that Barbie cannot handle with just one hand.  Fortunately, we had a stair-chair installed just 6 days before I fell and broke my hip.  I am using it regularly, and it does a good job hauling me up to our bedroom, the showers, and my office.

Since coming home, I have been hobbled by pain in walking.  The prevailing theory is that this is the result of the treatment I got last Thursday.  If the chemo is working, it is killing myeloma cells in the bone marrow, and the dead cells are the cause of the pain.  Friday I go in for another such treatment, and we are hoping it causes more pain by killing off yet more myeloma cells.  Meanwhile, we both feel as if we are one small false move from yet another disaster.  Our comfort cushion is the wonderful support of friends and family – THANK YOU ALL!

Crash!

Crash!  That was the sound of me hitting the floor at 5AM Friday morning, May 3.  I had gotten up out of bed to go to the bathroom, using crutches, as I had come to require either crutches or a walker to relieve weight from my painful right hip.  But I never made it beyond the end of the bed.  I must have blacked out, as I hit my head and neck on various pieces of furniture on the way down.  Barbie was up in a flash, and it was pretty clear I was badly hurt.  I simply couldn’t put any weight at all on my left leg.  We did manage to get my seat onto a walker so that I could get back to bed.

Clearly something was going on Thursday night/Friday morning.  I was cold all night long.  I just couldn’t generate enough heat to get warm in spite of being under a full load of blankets.  And then when I was on the floor Barbie took my temperature, and it was 102.5 degrees.  I probably had not paused to let my head clear after getting up because I was so cold.  Clearly a mistake.

Barbie called 911, and the EMTs arrived to transport me.  At first, they were reluctant to take me to Beth Israel in Boston, as that entails passing half a dozen hospitals perfectly capable of dealing with a broken hip.  But once my underlying disease was explained, they were OK with transporting me directly there.  They gave me a shot of fentanyl, as they explained that the ride would be pretty rough.  Then it took some pretty fancy maneuvering to get me onto a flat board and downstairs, as neither stairway in our house is a straight shot.  Luckily, I arrived at the BI Emergency Room pretty quickly.

Barbie joined me there, after necessary clean up from the accident, preparing the house to be abandoned for an unknown number of days, and taking our dog Otis to a kind neighbor’s. Then we had a pretty long wait.  They took x-rays and administered the normal batch of diagnostic tests.  But mostly it was just waiting.  There was a certain amount of ER drama.  A person in the stall next to me was out of his mind from drink or drugs, carrying on at the top of his lungs.  Eventually a number of large people overcame him, and they got something into him that quieted him down.

At around 3PM Jack Wixted, a surgeon in the Orthopedic Department, arrived to explain the he would repair my hip Saturday morning.  A decision was needed as to which repair alternative to employ.  The choices started with doing nothing, the choice for a 93-year-old with dementia.  The next choice was a pin and repair of the broken end of the femur.  Given that my multiple myeloma had probably weakened my bones, there was concern that there might not be hard enough bone to drill into.  Also, the fracture was further out on the head of the femur than my right hip fracture in 2010.  The third choice was partial hip replacement surgery.  This would be a much more intense operation, and there was concern about the blood levels I had been exhibiting over the last few weeks.  Yes, they could give me platelets and top up my blood with infusions, but transfusion/infusion results are never as good (or predictable) as using blood you generate on your own.  Long term, the results of the replacement surgery would be better, but the potential complications of a much longer, much more invasive surgery were a concern.

The decision was not clear cut, and Jack needed to consult with the oncology team.  We also called our physician daughter-in-law, Bridget Quinn, into the discussion, so Jack went away while all the players could be assembled for a consult.  About this time a doctor appeared, whose function was to survey people in the ER who may be feeling that they are being ignored, and find the resources to make their treatment progress.  We told him that 30 minutes earlier he would have found us in need of his services, but no longer.  He was still helpful, and since I have spent lots of time in the ER waiting for something to happen, I thought having a doctor specifically assigned to play that role was a welcome improvement.  At the very least, it shows awareness of the problem.

Eventually the consult happened, with a clear consensus for the middle option, the pin and repair.  Then it was a question of a room for the night.  Eventually I was transported to the Farr building and a room on the orthopedic ward.  The drama encountered there involved the mental state of my new roommate.  I assumed initially that he was on an extended cell phone conversation, as he was frequently making angry and emotional comments.  But it turned out that he was just afflicted with dementia.  The climax was around 4 in the morning when nurses had to come in and clean him up in multiple ways, since he had soiled himself and gotten blood all over everything because he pulled out his IVs.  I was very impressed by the patience of the nurses and their cheerfulness in the face of a major event that was anything but pleasant. 

I had the impression that I would be the first operation of the day, but I wasn’t transported down to the Operating Room until 10:30.  The Beth Israel operating room waiting area is impressive in its size.  Clearly it operates at a fraction of its full capacity on the weekend.  You meet the full staff ahead of time, so you have confidence in the anesthesiologists, nurses, and assistant surgeons who will work on you.  I actually went into the Operating Room itself at 11:45, and in no time flat, I was out.

I became conscious again at 2PM, and they said the operation went well.  The surgeon explained that there were no complications, that there was enough bone at the head of the femur to drill into, and that the bone was strong enough to hold the pin.  So, the broken hip was repaired with a minimum of drama, but that was far from the end of the story.

On Sunday, literally 24 hours post-surgery, a physical therapist came by to get me moving the left leg again.  The muscles in the entire leg were traumatized by the surgery, and moving it at all took major effort.  She had me get up out of the bed and into a chair.  They use a crane that is built into the ceiling above the bed to do that.  They put a sling under you and hook it up to the lift in the ceiling.  Then they pick you up like a sack of potatoes.  (Barbie thought I resembled a massive baby being delivered by a huge stork.) The sensation the first time is unnerving, as your appendage that was just operated on is deathly afraid of being moved.  But by the second move, it felt almost normal.The physical therapist gave me a list of 6 exercises to do.  At first doing even one was a challenge.  Now, on day op + 5, I can do most of them for the suggested number of repetitions.

 

An administrator came by and explained that physical therapy at the BI is primarily intended for evaluation of readiness for moving to a rehab facility.  She took our information and produced a list of 3 places quite close to home that provide the required services.  We now need to get serious about making that happen.

The second night with my demented roommate was a little less dramatic, but at 4 AM he did have to be cleaned up again.  At least that time there was no blood.  He moved on the next day, and he was replaced by another roommate that was much quieter.  His main offense was requesting Fox News on his TV.  Luckily, he had earphones, so we didn’t have to listen to it.  But he didn’t get the concept of the nurses call button, so when he called out for a urinal in the middle of the night, I rang my nurses call button and ideally prevented a mess.  But again, by late in the night the nurses had to be back cleaning things up.  I decided that the patient population in the Farr building is in much worse shape than the patient population I am accustomed to in the Hematology / Oncology ward located in the Feldberg building.  On Tuesday I was switched to the Hematology / Oncology ward on Feldberg 7, my familiar home here at Beth Israel.  I’ve never been immobilized while I have stayed here, so it has become clear to me now that mobility is a blessing.

A continuing concern was when would I be able to resume my multiple myeloma treatments.  So far, those treatments are still on hold.  It turns out that x-rays revealed that I had pneumonia in my right lung.  Perhaps that is why I was so cold and running a fever Thursday night / Friday morning.  The x-ray information could also signal the presence of a pulmonary embolism.  I’ve had 2 in the distant past and a hip fracture and multiple myeloma are risk factors for emboli as well.  So, all sorts of diagnostic tests have proved that what I have is pneumonia, not an embolism.  It appears that antibiotics have done a good job of treating the pneumonia.  For the first time, however, I ended up on oxygen, as it seems the pneumonia interferes with oxygen exchange.  Gradually, I was able to move away from requiring that assistance.

The myeloma treatment suppresses blood counts and impedes healing.  Had I shown up last Friday (as originally planned) and they detected the pneumonia, they certainly would have delayed treatment for a week.  The current plan is to get me into rehab and then resume the multiple myeloma treatments.  They did request a free lambda test, and the latest reading is 792.  The prior week was 584 and the week before that was 796, so it is going in the wrong direction, but not disastrously so.

For the next iteration of this blog I hope to have x-ray pictures of my hip pre- and post- operation.  I have access to a patient area of the BIDMC website that has information about x-rays, but not the actual images.  They have narratives of what was learned from the x-rays only.  Pretty boring.  Stay tuned.

Results!

Since the end of the CAR-T Cell clinical trial, I have had a variety of treatments and a variety of results.  First a batch of Cytoxan, which initially had a positive response, and then nothing.  Then Daratumumab + Velcade + Pomalyst.  While I was on the full dose, the results were positive.  But a severe rash cut the Pomalyst dose in half and low blood readings caused the Daratumumab to be skipped a couple of times.  The net result was that the multiple myeloma resumed its march.

Finally, I started a new treatment on Wednesday, April 17: Elotuzumab + Velcade + steroids.   Initially, my body felt as if it had had been slammed:  severe bone pain, much more restricted walking, severe cramps, frequent urination, extreme fatigue.  I spent most of 3 days napping, and then had no trouble sleeping at night.  Either I simply could not handle this combination of medicines or maybe something good was happening.  The first measurement of the results was a blood test taken the following Tuesday, though the were not available until that Thursday.  Here is a picture of the graph of Free Lambda, the key measure of my disease:

What had been a new high of 2604 is now reduced to 30% of that number, or 796.  To get results like that, I’ll take a body slam or two!  My reaction to a second treatment this week was much less severe.  In fact, I was thinking I was spared any pain for the first 24 hours, but then the impact hit.  My right ribcage feels as if someone kicked me with full impact.  If I sneeze, my whole chest suddenly erupts.  So ideally, more good things are happening in terms of disease reduction.

Googling “Elotuzumab mechanism of action” gives a number of links, including www.ncbi.nlm.nih.gov/pmc/articles/PMC5944582/.  There is a cell surface transmembrane molecule called SLAMF7 that Elotuzumab somehow targets, resulting in cell death of the myeloma cell.  I must have lots of SLAMF7 receptors which makes the Elotuzumab quite effective.  The course of treatment is 8 weeks of once-per-week treatments followed by treatments every 2 weeks.  Meanwhile I may or may not qualify to start the clinical trial of the vaccine treatment that my oncologist is heading up.  So, there are at least two irons in the fire to keep my disease at bay.

Meanwhile, we have had a Stannah stair chair installed.  This is a chair that goes up and down the stairs in the front of the house.  Ideally, I will not need to use it forever, but right now it is quicker to use the stair chair than to climb the stairs using crutches.  In effect it makes our living arrangement here into a single floor arrangement.  Unfortunately, those are the stairs our dog Otis uses to get to our bedroom, so having a chair halfway up initially threw Otis for a loop.  But Barbie did find a way for Otis to get by the chair, so he was able to join us last night, rather than whimpering at the bottom of the stairs.  He is a 94 pound yellow lab, so you can’t just pick him up and carry him around!

When your numbers are bouncing all around the place, it is difficult to know how you are supposed to feel.  In fact, I have felt pretty terrible, sleeping much of the days following the treatments.  But the positive direction of the free lambda has given me hope that had been missing while the disease was rampant.  Given how quickly the results can turn negative, it is difficult to put too much faith in the numbers, but for the moment, we have a definite schedule set up, which should make ordinary tasks of “living” more predictable and therefore a bit easier to manage.  Tuesdays in Lexington I will get an infusion of IV Fluids and they will take the blood for tests.  Then on Fridays in Boston I will receive the weekly treatment of Elotuzumab.  Ideally on Thursdays we will receive the results of the latest Free Lambda.  Ever lower, we hope.

All of this calls for lots of driving, with full exposure to Boston traffic.  I am no longer allowed to drive beyond the center of Stow, so Barbie is the usual chauffeur.  As treatments can be up to 5-6 hours and the IV infusions about two hours, not counting the commute, the disease is sucking up lots of time, as well as my well-being.  Barbie is still teaching, doing the chorus and trying to play some tennis, as well as pick up the slack for all the household duties I cannot do, as my movements are restricted to those things I accomplish with limited energy and using crutches or a walker.  Neither of us ever imagined we would be in this situation.

Sunday, April 28 marks the annual MMRF (Multiple Myeloma Research Foundation) 5-K race, which many of you have supported in the past.  In many ways, this event acts as a marker for the progression of the disease.  I ran the course in 2013, 14, 15, 16, and 17, winning a first each year in the “survivor” category.  (Very few “survivors” are able to run, so this is a testament to the destructive nature of the disease, not any particular swiftness on my part.)  Barbie also was a winner in the women’s category, ages 70 to….94!  Wow.  Last year I could not run, but pushed my youngest grandson, using his stroller as a walker.  This year, I will participate, but with a team pushing me in a wheel chair.  The weather promises to be cold, windy and possibly rainy, so the pushers will get some extra exercise.  Thanks to all of you who have supported this important organization in the past.  I am living proof that the research they are doing does make it possible to extend life.  As a participant in several trials and the beneficiary of many new medications, I am grateful for the ongoing work of the MMRF.

Bad News

The latest Free Lambda reading is 2018, up from 1755.  The hope was that the treatment of Cytoxan last Thursday would have brought that number down.  Not so.  It is not the worst reading ever, but the next to worst.  The general idea was to let the Cytoxan have its effect, and then start a new treatment of something called Elotuzumab next Thursday.  But given the latest direction of the numbers, I am now scheduled for a treatment of Velcade this coming Thursday.  Here is the latest graph:

Velcade has been effective in the past, but it has declined in effectiveness over time, as my disease has evolved around it.  But still it is better than just watching the numbers go out of sight.  The hope had been that my bone pain and hip malfunctions were the result of the various treatments having an effect upon the bone marrow, which at the last bone marrow biopsy was 80% plasma cells (the bad guys.)  If the treatments were having a positive effect, then there should have been a number of plasma cell cadavers messing up the bone marrow.  Apparently, that was an overly hopeful interpretation of what was going on.

Last week I spent the entire week in at Beth Israel.  My calcium and creatinine numbers were poor to start the week, and I was walking with crutches or a walker because I couldn’t put significant weight on my right hip.  They took all sorts of images of my hip and back and head.  The head because I had an episode of double vision, which presumably was just a distraction.  At any rate they gave me lots of fluids, and the kidney function numbers fell into line.  Clearly, I am just not drinking enough water to keep myself hydrated, even though I am making at least an honest effort to do so.  The week before we did discover that Beth Israel has a location in Lexington where we can get an infusion of fluids without having to travel all the way into Boston, so it is much more convenient, especially if hydration via IV is going to become a necessary part of the treatment.

The other issue is that my platelets are low.  So low that I do not qualify [yet] for the clinical trial Dr Nahas wants me to join.  The normal range is 150 - 400, and I hit a low of 19.  They were talking about making an exception because clearly the cause of the low reading it the Multiple Myeloma, but the review board decided to just delay my entrance into the trial until the platelets get back to 50. 

The dates start at the end of January, when things were normal.  Then they got low, came back, and then got really low.  But they are going in the right direction now.

Overall, I am feeling poorly, and I find it hard to generate much optimism.  My torso has general bone pain, and I am walking around with crutches because I cannot put weight on either hip at this point.   I am getting inured to pain meds, but the effect is that I take lots of naps and feel pretty useless.  Sorry to be the bearer of bad news, but that is the situation right now.  But things do change fast.  On Friday, when I was released from the hospital, I felt really good and ready to take on the world.  I certainly hope that returns soon.

The Hardest Yet

The period covered by this blog post has been the hardest period for me yet.  And that includes the Bone Marrow Transplant, which was a near death experience, and the Whipple surgery, which really took the starch out of me.  Either the underlying disease or the regimen of chemo that I am currently undergoing has really thrown me for a loop.  I have trouble doing stairs, I shamble around because my legs don’t work right, and I have a major energy deficit.  I would have written 2 blog posts instead of this 1, except I had no energy, and it turns out that producing a post takes some umph.

The good news is that when I am able to receive the treatments – Daratumumab, Dexamethasome, & Pomalyst – they do knock the underlying Multiple Myeloma down.  But they had to adjust the initial doses, as I was reacting strongly to the medicines, and as a result I ended up off the treatments for about a week.  During that week the disease sprang back to almost the level where it had been prior to the treatments, which was pretty high.

Enough of a pity party.  What’s actually gone on?  Here is the graph of my Free Lambda, the measure of my Multiple Myeloma:

Clearly in early February the disease took off.  The initial treatments of Dara, Dex, & Pomalyst brought it right down.  Not to normal levels, but at least close to where it had been during the CAR-T treatments.  But then reality intervened.  First, they were concerned about the blood tests that measure kidney function, Calcium and Creatinine.  [Kidney malfunction is one of the endgames for multiple myeloma.]  They were elevated and I was having an array of side effects, so they skipped the second week of Dara.  Then I got a terrible rash, so they decided that I needed a lower dose of Pomalyst, so they had me stop taking that as well.  And the disease popped right back up.  With the lower dose of Pomalyst and the resumed Dara, the progression has been down, but not quite as dramatically as at the start.  But you can see a downward trend, even if there is a pretty great variation in the measurements.

Meanwhile, just to make things interesting, other things have been going on.  On March 2 we hosted an Iranian dinner, which we frequently donate to a service auction at our church.  Since the prior Wednesday I had been feeling poorly.  I was way off my feed, and I took lots of naps.  I probably overate the Iranian food, as Barbie cooks some great dishes for that meal.  But almost as soon as the party was over, I was stricken.  Off to bed, feeling terrible.  Ditto the next day.  I felt incredibly bloated, and the Iranian food was going nowhere.  A snowstorm was due on Monday, and clearly I was not doing well, so Barbie was talking about going into the Beth Israel ER.  I tried to ignore her suggestions, but at 5:30 I threw up the bulk of my prior night’s meal, and we were off to the ER.  Long story short, I had a small bowel obstruction, which is where your intestine is blocked by a knot of scar tissue, and nothing is getting through.  The normal remedy is for them to stick a tube down your nose and throat and empty the contents of your stomach so that the pressure is relieved.  Vomiting at home and again in the ER had done a pretty good job of emptying my stomach, so I was spared the nose tube.  They gave me some contrast dye to see whether things were “open”, and they were.  But they kept me in the hospital for 3 days to make sure the intestine was healing and nothing more was going on.

All of which had nothing to do with multiple myeloma!  Just an opportune time for a random event to strike.  Presumably the scar tissue was the result of the Whipple Surgery I had in the summer of 2017.  It was just waiting around for me to be down because of the multiple myeloma.  Seeing me down, it chose to kick me.  Thanks.

That was just 1 of the 5 hospitalizations I have had since Feb. 8.  The other 4 have been the result of concerns about my calcium and creatinine levels.  It turns out that for me this combination of drugs leads to dehydration.  So I am supposed to drink 2 liters of fluid a day.  I never come close.  When I do, I feel bloated, almost like having another bowel obstruction.  But the result of dehydration is elevated calcium and creatinine, which sets off alarm bells.  Here is a graph of these blood tests:

Calcium is graphed against the left axis and Creatinine is graphed against the right axis, so the graphs line up.  The result is the normal max for each overlay the other.  So I go in for an infusion of Dara, they see high levels of Calcium and Creatinine, and they admit me to deal with the dangerous levels.  At first they gave me a medicine to reduce the level of Calcium, as well as multiple bags of IV fluids.  Later admissions they simply gave me IV fluids, which clearly take care of the elevated levels.  Meanwhile they would take x-rays, MRIs, CAT-scans etc., to diagnose my other ailments, none of which they ever found a reason for, other than general reaction to the chemo.  Or reaction to the underlying disease.  Take your pick.

There was an especially important time just recently when I was NOT allowed to be in the hospital: Barbie’s 40^th Anniversary Concert.  A crisis was simply not allowed.  Should they have decided to keep me, I was going to walk out AMA (against medical advice).  It never came to that because they gave me preemptive bags of IV fluids every other day leading up to the concert.  The concert was wonderful.  A complete triumph for Barbie and the Sounds of Stow Orchestra and Chorus.  And a sell-out to boot!  We had the requisite party here at home afterward, and I headed into Beth Israel for my Monday batch of fluids.  So I never even had to help clean up!

Along the way there have been various interpretations of events that I hope make sense.  One symptom I have pretty badly is bone pain.  Especially in my back and chest, the bones just hurt.  Dr. Nahas pointed out that my latest bone marrow biopsy revealed that my bone marrow was 80% plasma cells, the bad guys.  The normal level of plasma cells in healthy bone marrow is 5%.  If the chemo is successful in attacking the multiple myeloma cells in the bone marrow, the residue of the dead MM cells could be clogging up the bone marrow and acting septic.  So the pain may be a function of success!  But then again, maybe not as the free lambda numbers go back up.  At any rate that is a hopeful note for what I am going through.

In general it is pretty down to be feeling poorly, having no energy, and wondering what is going to happen with my disease.  But if the disease does come under control, then the travail will certainly have been worth it.  I am perfectly willing to take some body blows in order to bring the underlying malady to heel.  The problem is the element of doubt.  What if the disease evolves yet again around the current treatment and there is no light at the end of this particular tunnel?  What did Emily Dickenson say?   Hope is the thing with feathers - a crucial element in the emotional mix to get me through this episode.

As always, my family and friends continue their support and kind wishes throughout the ordeal. The doctors take time explaining things – but they just do not have answers, as the treatments available to me now are just too new to have generated meaningful data.  As a multiple-times-over loser, I now qualify for a Phase Two clinical trial in which a new drug is paired with a vaccine, in the hope that the combination will better attack the underlying MM.  I guess one positive in all this is that at least I can contribute to the advancement of knowledge about this disease.

A Little Drama

Last post, I was up in the air.  My Free Lambda was turning worse, but I was feeling well.  So things were indeterminate.  No longer.  The Free Lambda has gone into record territory.  Here is the Free Lambda graph through February 11, when a treatment decision had to be made:

Dr. Nahas directed a three-part treatment regimen: weekly infusions of Daramatumumab, daily Pomalyst pills, and supplements of Dexamethasome, a steroid.  These all started Friday, 2/8, and all seemed well.  Other than the after effects of a pretty bad cold, I was still feeling well, but the numbers were a real source of worry.  Dr. Nahas said if the numbers continued their upward trajectory, they would use apherisis to filter the bad guys out of my bloodstream, before they clogged up my kidneys.  This would be a band aid approach, as it is a response to an emergency situation, a way of preserving kidney function temporarily; obviously they would have to find a way of controlling the bad guys to avoid dialysis.

Well, before I could come in for my second weekly Dara infusion, I began to feel as if I was reacting to something.  A very itchy back, muscle cramping at the least provocation, shortness of breath, and a pain on the exterior of my left chest.  These symptoms started on Tuesday and became real on Wednesday.  I reported them to the BI staff on Thursday.  They called me back, and told me to check into the Emergency Room.  I suggested that I would get some things done that morning and drive myself in early that afternoon.  No, I was not to drive, and I was to come in right away.  They were concerned that I might have a cascading reaction that could be life threatening.  So I packed for a couple of days, and we arrived at the Emergency Room at noon.

The Emergency Room is basically slow motion chaos.  I wonder if they would have prioritized things so that they might have dealt more quickly with me if I really did have a crisis situation.  In fact, it took a long time to check in, then they took vitals and blood tests pretty quickly.  But then another hour + passed before I was led back to a bed.  Then it was more waiting.  Eventually they took an X-ray of my chest and put in an IV for administering fluids.  That was going to be in anticipation of a PET scan, but that never happened.  Finally I was transported to Feldberg 7, the hematology / oncology ward where all the nurses know me.  I arrived at 11:55 PM, but with check-in and various visits, it was 1:20 AM before I was actually able to get to sleep.  Then of course, they wake you at 4 AM for vitals and taking more blood.  Lots of incentives NOT to report anything out of the ordinary to the medical staff.

By this time I felt I had done the right thing, in spite of the travail of the Emergency Room.  Friday was the day I was scheduled for my second infusion of Dara.  They held off, pending another series of tests.  I had a lung scan to determine if the pain in my left chest was a pulmonary embolism.  They took yet more blood.  Bottles, not vials.  One wonders if the medical profession has never gotten over the idea of bleeding patients to relieve them of bad humors.  By this time the shortness of breath was gone, but Thursday/Friday night my left chest hurt more while just breathing in bed.  The medical team came by on rounds late in the morning, and they explained what the various tests were designed to tell them, but they had no answers at that time.

I had a late lunch, and then Barbie came in for the afternoon.  She brought underwear and supplies for the weekend, as at that time we just assumed I was a prisoner for the weekend (a 3-day weekend).  She planned to drive up to Vermont on her own Friday night, after the holiday weekend traffic had thinned out.  After all, I had heard nothing from the medical team, which to me meant no decision.  I actually sought out the doctor who had led the rounds that morning, and he had good news about the latest Free Lambda tests.  He didn’t say anything else, but maybe my asking about the results from the tests sparked something.  At any rate, Barbie & I were walking past the nurses’ station on the way out when Bridget, the supervising nurse said, “Oh, I hear you are leaving us!”

What?? We had heard nothing.  If the news had come 5 minutes later, Barbie would have been on the road, probably stuck in traffic, and not very eager to turn around and come back to the hospital.  Apparently the tests ruled out an embolism, and the results of the Free Lambda tests were very positive.  Here is the graph of my Free Lambda through Friday:

That is a pretty steep decline.  The value is still higher than when I was first diagnosed in 2012, when my body was falling apart.  But definitely going dramatically in the right direction.  That plus my overall vital signs were positive, and I had told various doctors that I wanted to make a special event in Vermont: a joint birthday party for 3 grandchildren, where they would be joined by the other 3 grandkids.  So our entire family would be together.  Apparently it is not uncommon for people to have a reaction to the Daratumumab, and perhaps my symptoms corresponded to that reaction.  Actually, I never spoke with any medical staff, so that is just a surmise on my part.  But I did not hesitate to get out of there as fast as possible.  I am to call in on Tuesday and arrange when the Dara infusions will resume.  Meanwhile, I am a free man.

In fact, I am writing this blog in the lodge at Pico Peak, where Barbie and Andrew’s family are skiing.  Skiing is one of those athletic things that I am resigned never to do again.  And sitting here in the lodge observing all the travail of putting on all that gear, and then seeing people come in freezing cold, I wonder if it is worth it.  But clearly the kids enjoy it, and Barbie likes to bond with the kids as they are learning to ski.  She used to give Tyler (who is now going to be 9) a day of skiing together, but now Tyler wants to ski faster than Barbie does, so he entertains himself skiing backwards and twirling around, while she comfortably winds down the slopes.  In the afternoon, Barbie shifted companions, skiing with Emma, who also looks like she has a great time.

Needless to say, this has been an emotional roller-coaster for Barbie.  She felt guilty dropping me off at the Emergency Room and then taking off so that she could teach piano lessons Thursday afternoon.  But Friday morning she had follow-up appointment for some previous dental surgery, but she felt guilty not being in the hospital keeping me company.  I told her how it was hurry-up and wait as the various tests would take me away for a while, and then leave me in the room for an extended period of time before the next event.  At any rate, she came in mid-afternoon Friday, assuming she would come to Vermont and leave me for the long weekend at BI.  And she was feeling guilty about deciding to do that.  I told her not to worry about it, but that had zero effect.  So the unexpected release was all the more euphoric, as our expectations were so much the opposite.  Even this late in life, our expectations are not always accurate, and there is ample room for surprise.

In spite of the very positive turn of events for my Free Lambda, the level is still concerning.  Measured on the scale that was in effect in 2012, when I was diagnosed, the latest number is 1407.  The equivalent number in June, 2012, was 1329.  But clearly something has Free Lambda going in the right direction.  Is that simply the new medicines I am on, or is it the result of those medicines waking up the dormant CAR-T cells that seem to have gone on strike since November?  If the treatment that curbs the underlying Multiple Myeloma results in an allergic reaction, I’ll take the reaction in order to control the Myeloma. 

The combined Vermont birthday party was a great success.  Andrew concocted a cake with different symbols for each of the kids.  Steve from Minecraft for Tyler, a horse for Emma, and a Leo for Gabriel, a character from his favorite video game, Leo’s Fortune.  All these attacking a group of zombies.  It was especially gratifying to see the Jamaica Plain and Vermont cousins playing together Sunday afternoon.  The energy level was incredible!  Whoever came up with the idea of replacing old, worn-out, malfunctioning beings such as us old farts with young, energetic, new editions was a genius.

Still at Sea

It has been 2 1/2 months since my last post, which seems like a long time.  I have kept awaiting definitive news on my disease, only to have a number of weird reports that leave things even more up in the air.  That is still the case, but I thought I would simply document the current state of play.

Back in November, when I wrote my last blog post, I was still hoping the second dose of CAR-T Cells would be the magic bullet.  Well, such hopes are no longer sustainable.  Yes, I am still feeling good, but the numbers tell a different story.  As of the last post, they spun a mixed, contradictory story.  Unfortunately, now they tell a consistent negative story.

Here is the Free Lambda graph:

You can see that Free Lambda actually went up after the 9/24 infusion of CAR-T cells.  But then it went down and bounced around a bit.  But after a month that included Christmas, it has gone up dramatically,  to a level that if confirmed, will probably lead to a new treatment.

The Bone Marrow Biopsy results are equally grim:

These numbers went down following the 9/24 CAR-T cell treatment, giving cause for hope.  But the values on 12/18/18 quickly erased that hope.  They are at the highest level since fall of 2017, and in a dangerous range.

We had a ton of questions for my care-givers at Beth Israel when we met with them last week.  Have my myeloma cells evolved so that the CAR-T cells can’t recognize them?  Do they still have the protein on their surface that the CAR-T cells are programmed to identify?  The company running the clinical trial (Bluebird Bio) takes 18 vials of blood periodically.  Do they have any idea what is going on?  Can they see if the CAR-T cells are still in my body?  If they are, why are they on strike?  Basically, we wanted an insight into the science of what is going on in my body.  We e-mailed the questions ahead of time, but during our meeting on 1/25, we didn’t get any answers.  Bluebird Bio has not shared anything with the participating oncologists.  They will reach out to see if Bluebird has any further insight, but they didn’t hold out much hope.  The general experience has been that the CAR-T cells last about 6 months.  And the average duration of complete remission is 11.5 months.  So the fact that in effect I got a year without any further chemo treatments is now being read as a good response – though far less that we had been hoping for.

Meanwhile I have been feeling quite good.  We spent 2 weeks in Hawaii, the first week with my two sisters and one of their husbands.  The island of Maui was really nice, and the family dynamics were all positive.  The second week we spent 4 days on the Big Island, touring inactive volcanoes and observing large fields of dark gray lava.  Clearly these lands are very recently created. 

I’ve also been feeling well enough to do myself some harm.  I chose to split some wood to fulfill a commitment made to the Sounds of Stow auction.  Well, it turns out the wood I was trying to split really didn’t want to be split.  I ended up pounding it like crazy with a maul, and then using a wedge and sledge hammer to actually get the wood to submit to my will.  At some point I felt something twinge in my left rib cage.  It didn’t feel like anything broke, but I did stop using the maul and sledge hammer.  Two friends with pickup trucks and I delivered the wood later that day, but I clearly was not as well as I was at the start of the day.  Then later that night, I discovered I could not sleep on my left side.  In fact, I couldn’t sleep in bed at all.  I ended up sleeping in the recliner I got last year when my back was in really bad shape.  I reported all this the next morning to the doctors, and they told me to come in for an x-ray.  I did, but the x-ray showed nothing.  Then I sneezed, and something at the bottom of my right rib cage performed the same trick.  At any rate, I spent 3 nights in the recliner before I could come back to my regular bed.  The moral of the story: rent a log splitter next time, you idiot.

So why do I feel so good, when the numbers say I should be significantly sick?  I have no idea, but I’ll choose to believe the way I feel.  The latest Free Lambda number (1277) has only been exceeded in May, 2012, when I was first diagnosed, and in the summer of 2016, when I was recovering from the Whipple surgery.  Both of those times, I was feeling bad -- in 2012 because of compression fractures, and in 2016 because a Whipple really takes the starch out of you.  Maybe now I am not feeling so fragile because of prior Zometa treatments, which strengthen your bones.

All of the above was written 6 or more days ago on 1/28.  Since then I have had a wicked bad cold.  I ended up staying in bed Wednesday + Thursday + Saturday and Sunday.   I fought Barbie, who wanted to take me directly to Beth Israel’s ER for evaluation, to a compromise, agreeing to go to a local urgent care facility, agreeing to head to the ER if they spotted any pneumonia, dehydration, etc.  They decided I have a severe sinus infection, so I am taking medicine for that and beginning to feel a little better.

Last Friday they took a confirmatory test for my Free Lambda.  It has come back, and it confirms the prior reading, plus.  In the new measurement scale, it is 994, which translates to 1421 on the old scale.  This is worse than the reading in June, 2012, when I was first diagnosed.  So you might describe my disease as “rampant”.  Other than the cold, I still feel good, but the numbers are at a level that really cannot be ignored any more.  I go in for a Bone Marrow Biopsy and a PET scan tomorrow, Tuesday.  Then on Friday I meet with Dr. Nahas, my oncologist, to determine what to do in the face of this discouraging information.   The latest Free Lambda graph:

The most recent number doesn’t just confirm the 1/23 value -- it jumps up at an even greater rate.  All the more troubling.  My last visit was disappointing because there were no answers to my scientific questions.  I go into this week’s meeting with treatment questions.  What will they do to attack my current disease?

Barbie says she feels as if she lives her life at the end of a bungie cord, never knowing how wide the gyrations will be, in which direction, or when they will occur.  We are very fortunate to live so close to Boston’s wonderful major medical facilities.  Surely I have benefited for years from the newest treatments as they become available in the form of clinical trials.  I hope they continue to provide new pathways as I seem to reach the end of each trail after this very clever disease figures out how to get around the latest the researchers are throwing at it.