Stunning Myeloma Marker Results

In the three weeks of this new three-drug regimen, Pomalyst, Darzalex, and dexamethasone (DEX), IgG has dropped 39%, from 1330 mg/dL to 807 mg/dL, in tests done by Mayo Clinic.  This spectacular result brings IgG to the lowest level I have seen since my diagnosis in 2003.  To confirm that result M-Spike dropped 33%, from 1.2 to 0.8 g/dL, also the lowest value since 2003, when it was measured once at 0.52 g/dL.

This appears to be a spectacularly good omen, but a few things temper my enthusiasm just a little:

1. Three weeks ago, at the beginning of the new regimen, my blood also contained about a half dose of a different monoclonal antibody, unnamed because it was part of a study.  That agent declines in strength with about a four week half life, and it had been about four weeks.  Thus I have actually been treated by a four-drug combination, with one drug half gone and gradually disappearing.  We don't know what will happen when it is entirely gone.  No one has done this before.

2. Just yesterday, after the blood was taken for these tests, we reduced the DEX and moved the day that I take it to the night before the infusion.  The goal is to reduce the side effects of the DEX, but going forward it might also reduce its benefit if we're unlucky with this change.

3. In any case, three weeks is just not enough time to evaluate a new regimen.  Stuff happens.

Despite all of this temperance talk, todays results are amazing and wonderful.  They have to mean something good.  In four more weeks the tests will be repeated, and we are hoping for more great news.  In the meantime, I'll get another infusion every week. It went very well today - again no infusion reactions.

Neutrophils 3700

I was guessing 1700 / uL, with a little false bravado, actually just hoping they would be over 1000, so I was shocked to see the smiling nurse with the printout showing 3700, nine times as many as yesterday's count of 400.  Yesterday the doctor and nurses were concerned about neutropenia, asking me how I felt.  Based on prior experience, however, I believed that the neutrophils were there all along, just not measurable for some reason.  After a good night's sleep they have to be teased out of hiding, or out of some other phase, or whatever neutrophils do.

Note: I am not a doctor - what happens to neutrophils overnight is WAY above my pay grade - I am making this up!  Sort of - here is an article discussing it.  Good subject for study, because I'm sure that there are people who DO know.

Anyway the threshold for proceeding with the infusion was 1000 / uL, so here we go full speed ahead.  I'm already in the chair, waiting for the prednisone to drain into me - the Darzalex can't be started for another hour after that.

These things happened between yesterday's blood draw and today's:

• Last night I took 20 mg of dexamethasone (DEX), and skipped one dose of Pomalyst.  I think this may be the most important factor in improving the neutrophil count.  This morning my fasting blood glucose was 143, normally about 90.  That is a proven DEX effect, of course, and I wonder if that alone can affect neutrophils.
• This morning I got up well ahead of the blood draw and ate a good breakfast, including two cooked eggs with a scrap of last night's salmon, plus uncooked strawberries, blueberries, cherries, and blackberries, with low-fat plain yogurt, every item organic of course.  In that mix we would find plenty of live bacteria, especially in the yogurt where it is intentional, and perhaps the food can cause the neutrophils to come out and play.  I really AM making that up, but it is consistent with the realization that morning blood draws are almost always fasting, and afternoon draws always follow one meal at least, usually two meals.  
• I did some short but intense adrenaline-pumping exercises this morning just before checking in for the blood draw:  Six flights of stairs, running up as fast as I dared and walking back down carefully, and as many pushups as I could do. 
• The blood draw itself was done at about 11:00 am, compared with 7:30 am yesterday.  I have always believed (and observed) that neutrophils are at least double at 1:00 pm from what they are at 7:00 or 8:00 am.  Now I am wondering if it might be more about the food than the time of day.  In almost 13 years of treatment I never thought of that until today.

Next week's blood draw is 7:30 am on the same morning as the infusion.  I will do everything the same as above, except the time of day.  If the doctor agrees I will eat a similar breakfast, too, even if the doctor has ordered a blood glucose test, because the previous night's DEX will screw that up anyway.  I may not skip the Pomalyst, either, because yesterday's low count was a false alarm.

We are still waiting for the results of yesterday's kit draw to show up on the Mayo Clinic patient portal.  This is a real-time post.

Where Oh Where Have My Neutrophils Gone?

In advance of tomorrow's planned fourth Darzalex infusion, the doctors did a CBC with differential today to see how my neutrophils were standing up to the Darzalex / Pomalyst combination.  Surprise!  Neutrophils were just 400/uL, where the reference range for this lab is 1800 to 7700 /uL.

In other words, my neutrophils measured less than one fourth of the value representing the very bottom of the reference range - the lowest count that I remember in almost 13 years with myeloma.  Doctors and nurses were all asking if I felt OK, because a low neutrophil count (neutropenia) can result in neutropenic fever, potentially a life-threatening condition.  In the past my doctors have stopped treatment when neutrophils dropped below 1000.

So what do we do about that?  I have a Darzalex infusion scheduled for tomorrow.

First, I don't believe the number.  I don't doubt the accuracy of the test (much), but I have a history of low neutrophil counts that probably weren't low.  The neutrophils are actually there, but they don't show up (at least not as neutrophils) in a CBC with diff.  In the past, I have used two "tricks" to make the neutrophils appear:

1.  Take the blood in the afternoon.  I have repeatedly found that my neutrophil count is at least double in the afternoon.  In lieu of afternoon, take the blood as late in the morning as possible.  Today's draw was at 7:30 am.
2. Do some physical exercise just before the blood draw.  One doctor told me that the neutrophils hide in muscle tissue and can be rousted by exercise.  Another doubted that they hid in muscles, but implied that they were there somewhere, just not appearing as white cells, and told me that it was actually adrenaline that made them come out to play.  We're WAY above my pay grade here, but either way a little high-intensity exercise could do the trick - I do several flights of stairs as fast as I dare, and one set of pushups, as many as I can.

Please note:  I AM NOT A DOCTOR.  And even though these two tricks do seem to work for me, doctors and patients alike have told me that they don't work for everybody.  Maybe they ONLY work for me.

A third "trick" is dexamethasone (DEX).  Not a trick, really, but my doctors seem to agree that DEX may actually support my neutrophil count.  As evidence I have had CBC's for three weeks in a row now, prior to this one, always in the morning and with no exercise, with neutrophils always comfortably within the reference range.  In each case I had taken 40 mg of DEX the night before or two nights before.  This time we moved the DEX by one day, so the blood draw happened to come first, and got this surprisingly low result.  I think the DEX might matter a lot IN MY CASE.

So tomorrow I will use all of the tricks.  I have taken my DEX tonight already, and skipped tonight's Pomalyst capsule.  I will get another CBC/diff at 10:30 am, after getting myself just a bit sweaty with exercise.  The doctors and I have agreed that a count of 1000 per uL will be the threshold, below which the Darzalex infusion will be postponed until the count gets back up to a safe range.  At 1000 or above we will proceed with the infusion and return to the regimen.

We also drew blood for the myeloma markers today: IgG, M-spike, and light chains.  That was a "kit," then sent by overnight express to Mayo Clinic.  Those results will come on line tomorrow and I'm mighty interested.

Three Infusions

Two at Mayo Clinic, and now the third at a highly-rated local hospital.  We have made twelve 200-mile round trips to Mayo in Rochester so far just this year, almost one per week, and I'm tired of the drive.  Of course I'll do whatever it takes to stay alive, and Mayo is indeed a world-class center for myeloma treatment, so that sounds like whining.  However, if the drive is not necessary, it is certainly more convenient (and safer) to have procedures like blood draws and even infusions done barely a 10-minute drive from home.  My current Darzalex (daratumumab) regimen calls for weekly infusions for eight weeks, then every other week for a while (if it works), and eventually once per month.

Mayo Clinic is a model of professionalism of course, and it's big, with at least two infusion centers that I know of.  By contrast the local infusion center is smaller with about a dozen chairs, most of them arranged in a circle, under the watchful eyes at the nurses' station.  But they're good.  After one infusion there, I would be hard pressed to choose one place over the other - I have no concerns about the competence of either.  This was the local hospital's first Darzalex infusion, so they literally went to school on it before I came, and they knew exactly what they were doing.  I know because I checked and confirmed everything they did, just as I had at Mayo.

My first infusion at Mayo took about nine hours, the second about six and a half, and this third local one a little over five and a half.  The amount of Darzalex is the same for each infusion, but the rate of infusion can be increased if the patient's experience with previous infusions is good.  See the Darzalex Dosage and Administration instructions. By luck I have experienced no infusion reactions at any point along the way so far, and as long as that continues, this third infusion will be the model for most or all of my future infusions, five and a half to six hours.

As many as two of those hours are not actually required by the infusion itself but by the preparation for it.  There are pre-medications (Tylenol, Benadryl, and prednisone), followed by a delay for the prednisone to take effect.  Just as important is the careful work at the pharmacy in preparing the half-liter infusion bag with the correct amount of Darzalex solution.

Local infusions will make my life a lot simpler, but control of the myeloma is what it's about.  In addition to Darzalex my current regimen includes Pomalyst 2 mg every night, with dexamethasone 20 mg once per week taken the night before the infusion, and an equivalent dose of prednisone with the infusion.  Next week the doctor has ordered a blood test kit that will give us a first indication of the effect of this regimen.  I'm sure interested.

Pomalyst and Darzalex

Darzalex (daratumumab) is a potent myeloma treatment by itself, but even more so when combined with Pomalyst (pomalidomide), and that is what my Dr WG wants me to have now.  I couldn't agree more.  Two studies that have benefited other people have failed for me, one after the other, and my IgG and M-Spike have increased.  Far worse, my most recent PET/CT shows five lesions in my bones including three scary ones in the spine, so it's time to bring out the big guns.

I've been taking Pomalyst again now for a month, 2 mg every day, with dexamethasone (DEX) 40 mg weekly, waiting for the drugs from the most-recent study to wear off, and Tuesday I received my first infusion of Darzalex.  That was an experience.  I have been SO lucky - more than 12 years with myeloma without any infusions EVER.  That ended last December, with the last study, because one of the two study drugs was an infusion, but Darzalex is in a class by itself.  This is NOT a complaint, because we myelomiacs do whatever is required to stay alive and running marathons (or whatever) and we don't whine about it, right?  This is just a report.

According to the manufacturer's Darzalex Dosage and Administration instructions, there is the possibility of an infusion reaction of some kind.  For this reason the infusion rate starts out low and builds up.  If any reaction occurs, the infusion rate drops back to the beginning.  Furthermore, the very first infusion is a special case - the infusion rate is very low indeed - and if the instructions are followed correctly it cannot take less than 6 1/2 hours.  With a reaction, it could obviously take longer.  A few weeks ago in Virginia Beach we attended a support group meeting where I spoke with two people for whom it took most of the day.  Then I spoke to a friend from our own support group who breezed right through it - didn't recall that it took 6 1/2 hours.

In addition to infusion time, some amount of time is required to prepare for the infusion.  Since I don't have a port of any kind the nurse had to find a good vein (I have lots) and set up the temporary port.  Then I was given oral Tylenol and Benadryl, followed by an infusion of prednisone (the pre-meds), all to reduce the likelihood of a reaction, and there was a little waiting for the Mayo Clinic pharmacy.  When the Darzalex infusion arrived, the drug itself (I think three 400-mg vials) was already mixed with a liter of saline, that bag covered by a semi-transparent shroud intended to keep light away from the mix.

At first my "vitals" were taken every 15 minutes, really just blood pressure and heart rate I think, not even temperature or pulse oxygen, but of course they always asked how I felt.  The 15 minute intervals became 30 as time went by, I had no infusion reaction at all, and I suppose the Darzalex itself took about 7 hours total, maybe a little more because the infusion pump stopped and beeped every time they needed to take vitals.  Added to other delays I was in the chair for almost nine hours.  I dozed a little (the Benadryl) but mostly talked to my sweeties and amused myself with the computer.  Easily the most physically relaxing day I've had in years.

My advice: Go with the flow, get an early morning appointment with nothing else on the day's calendar, and plan on a nice, long, but easy day. Bring stuff to do - computer, smartphone, Kindle, books, magazines, friends to talk with, even watch TV or sleep.  My sweeties brought me food now and then during the day, and even a Starbucks.

Mayo Clinic knows how to do infusions!  The nurse who started me out (Andy) very carefully wrote out the start times for each medication on a whiteboard, and a chart of the specific settings for the infusion pump for each hour of the Darzalex infusion.  All of the nurses referred back to that chart as the day went on and shifts changed.  I wish I had taken a picture of the whiteboard.

Unfortunately for us Mayo isn't next door, it's about a 200-mile round trip, but we have an infusion center within a short walk of our house.  Darzalex infusions are weekly for the first eight weeks, then every other week for a while, and although I have appointments for three more infusions at Mayo I also have an appointment with a local provider to see if the infusions can be moved next door.  Mayo would, of course, continue to be my primary source for overall management of the myeloma.

We know that after seven wonderful years on Pomalyst my myeloma finally progressed, as we knew that it would eventually. A PET/CT revealed a hot spot appearing in one vertebra.  According to my doctors, that is probably a sub-clone of the original myeloma, somewhat immune to Pomalyst.  I was then taking Pomalyst as a single agent, and according to one doctor it's possible that the new clone could have been managed for a while by the simple addition of DEX to the regimen, but now after the failed studies it appears that we need both DEX and a third drug to manage the clone or clones.  Dr WG suggested that if this regimen gets my numbers down nicely, and the hot spots disappear, then perhaps Darzalex could be my next seven-year treatment.  Wouldn't that be something?  82 years old, getting monthly infusions, and maybe even still running a marathon now and then.  Dream big!

Better DEX Experience

Three weeks ago I whined mightily about taking DEX.  The worst problem was acid reflux the second night after taking it, but there were other issues too.  I'm happy to say that I have had better experiences since then.

Acid reflux:

Lots of good people offered great suggestions regarding the heartburn (acid reflux).  This formula has worked for three weeks in a row.  After the worst heartburn of my life, now zero heartburn:

• I take the 40 mg of DEX with food at the Sunday evening meal, and the reflux happens (happened) Monday night.
• No food at all in the last few hours before going to bed Monday night.  I figure two hours may be the minimum, although I have not tried less than three.
• No beer or other alcohol at all Monday.
• No chocolate after noon Monday.
• No coffee after noon Monday.
• Take a Zantac with dinner Monday night, but no other time.
• Take calcium citrate 250 mg twice daily every day.  No other calcium works the same.
• Drink some extra water if there is even a hint of a symptom after dinner Monday night.

Other:
        

The sleeplessness on Monday and Tuesday nights has improved too - I guess my rickety old body is getting accustomed to the DEX once again.  I'm still hyper on Monday and grumpy on Tuesday and Wednesday, but getting better.
     

It's not like I haven't taken this stuff before!  My Mayo doc is hoping to get me down to 20 mg and reduce it from there if the new regimen does the trick,  More about the new regimen in the next post.