Saturday, August 20, 2016

Intro To My Story

This is the story of my finding out I had an incurable and lethal form of leukemia. It starts in early 2002. I've been lucky, as I've lived more than twelve years with the disease, which is longer than the average longevity for a lot of folks. I never thought I'd live this long! This story starts out with a series of messages I sent to my family regarding my illness, before I even knew what I had. Then it goes through a lot of anguished and fearful messages as I realize what I'm dealing with. You see, my dad died of the same disease after having it for five years. These short messages start in February and go up to about July 2002, when I started my first round of chemotherapy.

When I finally started my first round of chemotherapy in July 2002, I began a journal, at the suggestion of a colleague, which I sent out to concerned friends and family. I included a lot of medical information about the disease and its treatments, my fears about my future and what was going to happen to my wife when I died, plus a lot of personal information that concerns things not generally discussed in public; my depression, references to sexual dysfunctions, side effects, diet and weight problems and, uh, excretory problems (all in good humor of course, without many clinical details). I'm a physician so I'm pretty open with these things. They're what I dealt with in caring for patients for decades, after all. There are many deep, thoughtful passages about death and dying, but there are also a lot of very humorous references about my treatments and my many misadventures (such as the time I accidentally pulled a central line out of my chest while in the shower--"Dumb ass!" I called myself) that I experienced during my therapy. There's rare bawdy humor, too, but I tried to restrain myself, not being sure exactly who was reading my stuff. You may find some of these things interesting, funny, sad, boring, too clinical, or whatever. It kinda reads like a book, and each "verse" (as I for some reason listed each passage) tends to build on the previous ones. Our daughter convinced me that e-mails were "so last-century" and she encouraged me to start this blog. So here ya go!

It presently consists roughly of seven sections starting with the compiled messages to my family from early 2002. The divisions between are roughly as follows:
Prologue-- early 2002 up to about July 2002.
Book One-- The First Chemotherapy Experience, July 22, 2002 until October 2003
Book Two-- Relapse, and The Second Chemotherapy Experience, With Stem Cell Collection, October 2003 to about October 2004 with a few updates thereafter
Book Three-- Starting in February 2008, More Chemotherapy and Some Experimental Stuff, with introductory information in the letters leading up "Book Three."
Book Four--It's Baaack! Starting March 2010.
Book Five--PCI 32765; the Bruton's tyrosine kinase inhibitor. Starting March 2012
Book Six--Venetoclax. Starting about August 2016

I welcome e-mail questions and frequently have addressed them openly in my letters which have been sent out across the US, Germany and Scotland to many concerned friends and family. I can be reached at

I hope to use this blog to keep all you folks who are reading this updated from time to time as I progress into my adventure and experience more and different treatments.

A DISCLAIMER: This is rather like the old TV ad that went, "I'm not a doctor but I play one on TV." When this series of stories started many years ago, it was sent exclusively to close friends and family. Gradually it was resent to more and more folks who had an interest in how I was doing, until I had a couple hundred folks or so on my mailing list. But, then my kids convinced me that it would be easier to put it all on-line so that all my correspondents could access it more easily. And, in fact that has happened. But what has also happened that, through the miracle of Google searches, many, many people around the world, who have an interest in CLL, have found my stories and have inquired about how I'm doing and asking questions or for advice on what they should do, as many of them also have CLL. I welcome these questions and inquiries but I must state that, though I have been dealing with CLL for almost 13 years now, and am a veteran of multiple kinds of treatments, and read a lot about CLL, and am a physician as well, I can't really be considered an "expert" on CLL. I am very happy to help folks go through their options and offer what I think is accurate advice and information about current treatments, but there are so many variations in this disease, and so many factors to consider, that I must make clear to anyone reading my stories that my advice is just that, and cannot be considered a clinical recommendation. Any options for treatment must be discussed with your doctor, and hopefully, with a leukemia expert. When I read through the papers presented at the clinical oncologist meetings, I am overwhelmed with the amount of information about my disease that I don't understand. There is so much information out there that no one person can know it all, especially a retired OB-GYN doc like me. But, I sincerely will try to help anyone who asks to understand what their options are and help them to know what questions they ought to ask before beginning treatments. Thanks for taking the time to read through all this!

Friday, August 19, 2016

Ramping Up The Venetoclax

Dave’s Great Adventure
Book 6, Chapter 1, Verse 2

The Muses have not been kind to me.

For almost two weeks I have been trying to get the second part of my venetoclax story written and sent. I have written, revised, rewritten it and then decided my stuff was too detailed, tedious and boring. I rewrote the whole thing, only to lose it to a power surge during a thunderstorm. Arrgh! So I’ve modified a previous version and here it comes. Here’s the deal; if you’re interested in the problems we encountered in just trying to get into the trial, keep on reading. But if you’re just interested in the venetoclax study itself, skip down to the “Ramping Up the Venetoclax” part.


I met Doc Thompson in the first week of May and that’s when he signed me up for the venetoclax study. That was quick and easy. It also turned out to be just about the only quick and easy part of this process. He introduced me to our hard-working research nurse, Blanche, who was in charge of integrating me into the study protocol. Blanche immediately started butting her head against several walls. She had to get approval from our insurance carriers to get me into the study, then try to get permission from the sponsor to waive having to repeat all the preliminary tests I’d had done just nine weeks previously, make appointments for any tests I still needed to get done and then, finally, when all this had been done, she had to get the sponsor (in this case, Abbott Pharmaceuticals or their biologics branch, AbbVie) to review my labs and other studies and agree that I was fit for the venetoclax protocol. We thought it might take a couple of weeks. It took over a month!

Blanche first had to get insurance approval for me to be in the study. Yes, when you’re in a research study, the drug company will pay for the “study drug,” and also for any strictly research tests that are done in connection with the study (like drug levels in your blood, etc.) but your insurance is expected to pick up the tab for any “routine” testing which has to be done. But I had just had a battery of expensive tests done within a couple months of signing up for the venetoclax protocol. Remember that I had a couple days’ worth of tests, including the bone marrow biopsy, CT scans, EKG, echocardiogram, numerous blood tests (you can’t believe how much some of these specialty blood tests cost) and more when I signed up for the nivolumab study in March. Would insurance pay to get them done again? Would the sponsor waive the requirement to repeat them after such a short period of time?

Blanche thought it might take a few days to a week to get the insurance approval. But it took a couple of weeks or more. I didn’t like the waiting. I was getting worried, seriously worried about the progression of my disease. By now I had been relapsing for something approaching nine months. The daily aching of my lymph nodes in my armpits reminded me that I was sick. I worried out of proportion to the length of time it was taking, but I now knew that some 17p folks like me have “explosive” relapses when they fail the drug and I also knew that I apparently only had a 60% chance of responding to the drug in the best of circumstances. In other words, I had a 40% chance of dying fairly soon. I was getting physically ill with these thoughts. But, there really wasn’t much else to do. I was scared. I feared that something was going to happen while we were waiting for all these approvals which would knock me out of the study.

After anxiously emailing Blanche a few times, inquiring about the (to me) prolonged time it was taking to get the insurance approval, she finally got it a couple weeks later. Great news! But, meanwhile, the sponsor refused to waive any of the preliminary studies. So, I had to be scheduled for all of the ones I’d just completed plus more. Blanche ran into a scheduling nightmare trying to schedule, again, manifold blood tests, a PET scan, the echocardiogram, EKG, another bone marrow biopsy and more.

Up until recently it had been fairly easy to schedule things like that, as each nurse could apparently do their own scheduling. But, in March of this year M. D. Anderson inflicted a new electronic records system on the staff. Ostensibly this is to make everything easier for the staff. In practice, it has made so many things harder, slower and more complicated for them and the patients, too. I could write a whole chapter on the changes I’ve seen at M. D. Anderson just in recent months. I love the place. I love the staff. But I have found myself getting angry with “the system” and how staff and patients alike have been getting jerked around in recent months. Appointments appear and disappear randomly, tests ordered never make it to the lab, medication orders don’t find their way to the pharmacy. Sometimes the computer doesn’t even know where we’re “authorized” to get our blood pressure and weight taken, as if it should make any difference at all. But that’s all I’m going to say in these pages.

Blanche set about trying to schedule all the needed tests, which required a great deal of coordination, some tests being able to be done only after others had been completed. She worked, I worried. Days went by, another week went by. Finally, we got a phone call from Blanche. It was about 5:15PM and we were watching the news. The stars had aligned and she had everything scheduled for me. She told us we needed to be in Houston THE NEXT MORNING to start the three days of required tests and scans! We threw some clothes in our bags and headed out, making hotel reservations en route. We didn’t arrive until after 11PM that night, but I was oh-so-glad to be getting going on the study. This was the start of seven consecutive weekly 600 mile round trips to Houston.

Getting the testing done was actually fairly straightforward and, except for a lot of wasted time sitting around, went well. People in the know at M. D. Anderson tell me that the “M. D.” in the name stands for “Most of the Day.” There can be a lot of waiting at many appointments, but I’m happy to wait. I was very happy to get the testing behind us because Blanche had me scheduled, finally, to start the drug the following week, the first week in June. After completing all the required tests, we left for home on Friday, with plans to return the following Monday, with the drug trial to begin on Tuesday.

After just enough time at home to wash clothes and get some cash, we headed back down I-45 on Monday. Our appointments hadn’t yet been made but Blanche was going to set them up as soon as the sponsor looked over my test results and gave the final approval. We waited for the call to let us know what we were supposed to do. We got the call while in the hotel room in Houston, on Tuesday morning, but it wasn’t the call we wanted. Bad news. The start of the drug testing had to be postponed. My tests were still in processing and weren’t yet ready. “Go home,” we were told, and we’ll try again next week.

Home we went, now waiting for yet another call to let us know that everything was ready. The call came. More bad news. Abbott/AbbVie wasn’t happy with the PET/CT scan, which had been done without IV contrast. We’d have to repeat it, this time with some sort of iodine contrast material (which is injected into a vein at the time of the CT scan). To save us yet another trip to Houston, Blanche added this additional CT scan on to the next week’s schedule, on the Monday before I was to start the protocol. We came back the next week, did the CT scan with contrast and everyone was now happy. We were finally in!


Venetoclax is a great drug. It’s a powerful drug. It’s too powerful to be used casually. In its early studies, some patients died. Doctor Thompson tells a story of one of the first patients he treated with venetoclax in the early trials. The patient had a white count of about 100,000, high, but not unusual for a CLL patient (normal white counts are about 6,000, +/- 3,000 or so). The standard dose of venetoclax is 400mgs, but to be careful, they gave this patient only a half dose; 200mgs. Eight hours later the patient’s white blood cell count was only 1,000!

SCIENCE LESSON FOLLOWS: Let me explain what that means. It does NOT mean that, in dropping from 100,000 to, 1,000, the drug killed off 99,000 white blood cells. When you have a number in your blood tests, like the 100,000 number above, what it means is that the test shows there are 100,000 white blood cells per every milliliter (or “cc,” they’re the same thing) of blood in your body. The average adult has about five liters (or 5,000 milliliters) of blood in his/her body. So, a white blood cell count of 100,000 means that person actually has 100,000 white blood cells/ml x 5,000mls of blood in the body, or 5,000,000,000 total white blood cells. That’s 5 BILLION white blood cells! So, in this case, when the venetoclax rapidly dropped this patient’s count from 100,000 to 1,000, it actually had rapidly killed off about 4,950,000,000 white blood cells, give or take a few dozen, in just a few hours.

That’s all well and good, but all those dead cells and their contents have to go somewhere. These cells have proteins, electrolytes (like potassium) and a lot of inflammatory chemicals. These things can clog up and damage the kidneys, cause heat rate irregularities and more. They can cause what’s called “tumor lysis syndrome” (TLS). That’s basically just dissolving too much “tumor” in too short a time for the body to handle the debris (this can happen with other drugs and other tumors as well).

I mentioned that a number of patients have died as a result of being treated with venetoclax. That’s not good news, obviously, for lots of folks. So, to minimize this very significant risk, the drug manufacturer has wisely made it hard to give the drug to CLL patients. It has put a number of restrictions of who can give the drug and how they can give it. First (as I understand it), any doctor who is going to give the drug has to go through specific training sponsored by the manufacturer. Secondly, those patients who are to receive the drug and who are considered to be at “high risk” of TLS, must be admitted to the hospital during the early stages of therapy so they can be very carefully monitored (described below). Those not admitted are still required to be carefully monitored with additional blood testing and exams. In every case, the drug is initially given in very small doses and “ramped up” very carefully and deliberately over five weeks.

I was considered to be “high risk.” Anyone with a white blood cell count over 25,000 or an enlarged lymph node over 5cms (about 2 inches) in size was defined as high risk. My white count was 34,000 and I had at least one node that was 8cms, or about three inches in diameter, among the dozens of enlarged nodes I had in my belly, chest, neck and under my arms. So, I got admitted to the hospital to start the drug.

While in the hospital I had an IV going continuously, giving me an extra two liters (about a half gallon) of fluids every day, plus the fluids I got in my diet and all the water the nursing staff kept pushing me to drink. I also got to collect all the “output” for them to measure, in a process I called “Operation Golden Flow.” They needed to know that all those fluids were coming out and not building up in my body somewhere. All this was designed to make sure my kidneys were working well and dealing with the cellular debris which was being created by the drug.

And I got stuck a lot. I had labs drawn before I took my first dose of the venetoclax and then every four hours for 12 hours, followed by several other tests during the next 36 hours. This was to check for any early signs of TLS and to look for how well the drug was working. I also had more tests before and after my second dose the next day.

I have mentioned how carefully and deliberately the drug is “ramped up.” This is how we started. The standard dose of venetoclax is 400mgs per day. For a new patient, the initial dose, given for the first full week, is only 20mgs. That’s only 5% of the standard dose. But, even at that miniscule dose, it started working. Within days, I could feel my nodes first swell a bit with inflammation induced by the drug, and then start to shrink.

I was discharged from the hospital after about 48 hours or so, and after another blood count the following day, we went back home, with me taking the 20mgs daily at home. But we came back in a week and I was admitted yet again, with the same routine except that this week my dose was increased to 50mgs daily. Same routine; blood tests before and every four hours after the drug was given, the IV going continuously and measuring all my urine output. Thereafter, I was allowed to increase my dose, weekly, as an outpatient, going from the 50mgs dose to 100mgs, then to 200mgs and finally to the final 400mgs dose, each time staying at the new dose for one week. And each week we were back in Houston for exams, labs and follow-up. In fact, every time we increased my dose I had blood tests done before the new dose, then 8 hours later and again in 24 hours, before being allowed to take the second dose of the new amount. They were exceptionally careful. And I’m very happy about that.

I’ve now been on the venetoclax for about 10 weeks. My white count now is actually low, but adequate. My red cell count has come back from being a low 28% (normal for a male is more like 45%) to the mid-30s. And my clotting cells, the platelets are back up to 100,000 for the first time in years (normal is 150,000 to 300,000 or so, but 100,000 is more than adequate for clotting). All the nodes in my armpits have disappeared and I presume the ones in my belly have too. And I can report that there few to no side effects. No joint pains like the ibrutinib caused, no hair loss, no rashes…nothing but some minor fatigue. Good news all around. I guess.

When I first started on the venetoclax in June, even before my first hospital admission, Doc Thompson mentioned in passing that at some point we should probably talk about a stem cell transplant. Now, I know that I may have to cross that bridge sometime in the battle against my disease, but I didn’t expect it to be very soon, since the venetoclax holds a lot of hope for folks like me. But, after just two months on the drug, he mentioned, more strongly, his interest in having me see the transplant team, so well am I doing. Everything is going just great…and he wants me to see about getting a transplant!

But for a transplant to have the best chance of succeeding, I need to be in a good remission. We will soon see how good a remission I am in. To that end, on August 23rd, which is our 47th wedding anniversary, I will be face down on a procedure table at M. D. Anderson with a large bore needle stuck deeply into my hip, drawing out some bone marrow to see how much disease is left in there. I’ll also be getting more blood tests and CT scans of my belly, chest and neck, looking for tumors. We’ll see, very soon, what shows up and where this will lead.

Next: The rationale for going for a potentially risky transplant while you’re doing just great on a newly approved drug!


“If you think health care is expensive today, just wait until it’s free.” P. J. O’Rourke

Sunday, August 7, 2016


Book 6, Chapter 1, Verse 1


“Life is a crooked line. It’s rarely what you plan.” –Chuck Slaughter, founder of TravelSmith

Or, as I’ve quoted many times before in this long story, “If you want to hear God laugh, tell Him your plans.”

Indeed, my life and plans have not been a straight line. I have settled in several times to write an update to my story, only to have our plans change…over and over again in the past six months. I will try to tell you of all these permutations of our plans in a somewhat condensed form, but those long-time readers of my stuff know that it is hard for me to tell stories succinctly. I always seem to render them in excruciating detail. I can’t help myself. Hey, I diagnosed myself with “hypergraphia” several years ago. I guess it doesn’t heal itself!

Last January it looked like I was relapsing. The folks at M. D. Anderson made plans for me to get a huge number of tests and to return in a month for follow-up. And indeed, on my return a month later, the manifold tests showed that I was indeed relapsing, that I was failing my wonder drug, ibrutinib. I’d long known that it was possible to relapse on ibrutinib, but I had done so well for so long, I was thinking I’d have many more good years on this drug. I knew of some folks who have been on it five years or more and continue to do well. I’d hoped to be one of them.

But, since I was relapsing, we had to come up with a plan for my next treatments. I mentioned at the end of my “Book Five” that Doc Keating was considering trying the checkpoint inhibitors on me. To that end, I was signed up for a clinical trial which combined the ibrutinib with a checkpoint inhibitor called nivolumab (trade name Opdiva) which is already on the market and shows success against lung, kidney and melanoma skin cancers. It had not, however, been used against leukemias except in a very few small trials. But it looked promising.

In February, I signed all the appropriate paperwork usually associated with clinical trials (laying out all the known and unknown risks). I also was scheduled for a whole raft of new tests to make sure I was eligible and qualified to be in this clinical trial, for which you have to be sick enough, but not TOO sick, to get in. The tests, which were scheduled for early March, included about a dozen tubes of blood being drawn, another bone marrow biopsy, CT images of my abdomen, chest and head and neck, an EKG and, finally, a cardiac echogram. I believe just getting eligible for the study set my insurers (the taxpayers of America—thank you very much!) back about $10,000 or so. All the tests went well so I was scheduled to begin the trial, which was the nivolumab in combination with my recently failed ibrutinib, later in March. But let me digress for just a moment in telling this story.

Initially I had great interest in getting into the nivolumab plus ibrutinib study. It sounded exciting (any drug that can help you stave off certain death HAS to be exciting, I think) but the more I thought about it, the less I liked the idea. I could find close to nothing in the medical literature showing that nivolumab had significant effects against CLL cells, and I knew already that my CLL cells weren’t responding to the ibrutinib any longer. “What was the point,” I thought to myself. But, I was scheduled to begin the study at the end of March and we went forward with the plan.

Then the trajectory of our plans went sideways. Our family had a long-planned trip to Alaska set up for mid-March, just before the start of the “nivo” study. We were headed to Fairbanks, the better to see the Northern Lights, plus we had plans to go dog sledding, snow-machining, flightseeing and more. We had a wonderful time up there as I mentally prepared myself for the upcoming study to start.

But, as we flew home from Alaska, I developed a fever. Followed by shaking chills. Followed days later by a persistent and vicious cough. I thought I had a bad cold. After about ten days of this, it was time to go back to Houston to start my new trial. There I saw my nurse practitioner, Jackie, who asked some questions and listened to my chest for a few seconds. “Do you want to be admitted?” she asked. “Hell, no!” I responded. I still believed I had just a bad cold and maybe a little post-viral bronchitis. But Jackie ordered a chest X-ray. It showed “double pneumonia,” pneumonia in both lungs! When the X-ray results came back, Jackie told me-- didn’t ask me-- “You’re getting admitted!” They ended up growing both the bacterium Pseudomonas and the virus human meta-pneumovirus out of me.

And so it was that I spent April Fools’ Day on the 16th floor of the M. D. Anderson hospital wing. Unlike the long-ago April Fools, who were celebrating New Year’s Day in April, not yet having heard about the change from the Julian to the Gregorian calendar, I knew the correct date. I just didn’t know when I’d be able to start my new study drug, the “nivo”. I was sick enough that it couldn’t be administered, but I really wanted to get going with something. I could feel lymph nodes in my neck and underarm areas growing, seemingly on a weekly basis.

But the study was postponed while I was tied to a hospital bed with an IV pumping in industrial strength antibiotics I’d never heard of before (ever hear of linezolid or cefepime?). I spent four days on the ward and then another five weeks on various oral antibiotics, trying to get well enough to start up the trial of nivo. All the time I was impatient to get going on the study. My nodes were getting bigger all the time and aching daily.

Then the trajectory changed again. I went back to M. D. Anderson in early May to see Doc Keating to see if I was finally well enough to start the study. We were running out of time, as the cluster of tests I’d done in early March were going to “expire” after 60 days and those days were about used up. But, Doc Keating wasn’t there. He was out recovering from back surgery, having been involved in a freak incident. As I hear it, there had been a car fire in the hospital parking garage and someone, driving too fast to get away from it, almost ran Doc Keating down. He dove out of the way, injuring his back and ended up requiring surgery.

So, instead I saw his protégé, Dr. Phillip Thompson, another Aussie who specializes in CLL and who is being groomed to take over for Doc Keating. Doc Keating is now working part-time and is slowly, very slowly heading into retirement. It was great to meet Doc Thompson after having only heard about him from other patients lately. If you see any of the patent Power videos concerning updates in CLL, you’re probably seen a lot of Doc Thompson in recent months.

Dr. Thompson examined me, felt the enlarged nodes in my neck, under my arms and in my belly (he could tell they were there though I could not) and we talked about the nivo study, for which I was still signed up. But Doc Thompson said that the early results of that study weren’t encouraging, that the response rate wasn’t very good. He felt that it was disappointing that they weren’t better, because in theory the nivo should be a great treatment for CLL. But, since it wasn’t working out well, he suggested I enter into a study of another drug called ABT-199 (also known by its generic name, venetoclax).

I’d been hearing more and more about venetoclax lately and in fact, knew that it had been approved for certain CLL patients just the month before. It’s been in development for about as long as ibrutinib, but some early problems in its testing phase set it back. This stuff really works! It works, maybe, too well in some cases. There were a few deaths of some patients early on because this stuff kills off CLL cells so fast that the cellular debris and the inflammatory chemicals in the CLL cells overwhelmed some folks’ kidneys and immune systems in a condition called “tumor lysis syndrome.” It’s nothing to mess around with.

I was happy to hear that I could sign up for a venetoclax study. I had actually wanted to get into one the previous February when I signed on to the nivo study, but there were no venetoclax studies open at the time. I knew it was a wonderful drug for CLL and I also knew that the docs administering it were exceptionally careful in giving it now, knowing full well the deadly complications it could bring on. And so I signed on to the study.

Only then did I go looking for recent updates on the drug and folks in my condition. You will remember that I have the deadly 17p chromosome deletion and I also now have failed the ibrutinib after more than three years. I looked up recent studies of folks like me who were taking venetoclax. There was one such study. It flatly stated that patients who have this chromosome abnormality AND who have failed ibrutinib have a “dismal” prognosis. They had recently started a study using venetoclax on some of these patients. At the time of publication they had signed up 18 study patients. Four of them were already dead six months into the study. And, the overall response rate was said to be about 60%. That left 40% of those patients with little hope. That scared me. It really scared me. So, as I entered into the study I wondered if I’d be one of the lucky 60% who at least showed some response to this drug, which apparently was now my last and best hope for survival, or whether I’d be one of the 40% for whom there would be little hope.

--Next; slowly and carefully starting the venetoclax…and maybe a transplant?


“Experience is the comb that life gives you after you’re bald.” –Chinese proverb

Saturday, January 16, 2016

Relapse After Four Years on Ibrutinib

Dave’s Great Adventure
Book 5, Chapter 2, Verse 12
January 12, 2016

Well, we had a great run, didn’t we, ibrutinib and I? I’ve been using the stuff for almost four full years and it has done wondrous things for me. I was pretty sick, with an aggressive mutation of my CLL. I had a white count of almost 100,000 and large, swollen lymph nodes throughout my body, including masses up to about 8 inches in diameter in my belly, chest, neck and under my arms. Life expectancy without treatment was said to be about 16 months or so at that point. Wow.

When I started on the Phase1/2a study of ibrutinib, in April 2012, the researchers had just completed a study on the first 110 patients and needed 40 more for the next step. I was extremely lucky to have been given one of those 40 openings. I was added on to the second phase of the study which added the anti-leukemia-cell antibody, Rituxan. I’d had this drug before with most of my other treatments, but never before in such close-together doses, as I was treated with the stuff weekly for the first five weeks of my therapy before backing off to four more monthly doses. It and the ibrutinib worked spectacularly well. I honestly could tell it was working within the first week. I could feel the pressure being taken off my belly as the tumors rapidly began shrinking. I was amazed and thrilled!

Within months my white counts normalized, my bone marrow biopsies were close to normal and my CT scans showed the tumors melting away. I was in clinical remission. And everything stayed stable with normal white cell counts from that point on. My low platelet count didn’t come back to normal, like I’d hoped, but just about everything else did. I began feeling fairly normal again. And just as I had during past remissions, I started forgetting I had the disease. It didn’t seem to really be a part of my life anymore, so well was it suppressed. Kathy and I have felt that way before, as if it no longer existed.

But we know better. CLL is an insidious disease. It almost always comes back, and every time it comes back, it tends to be more aggressive. The remissions tend to get shorter and shorter. But in between these relapses you start to feel pretty good and can almost forget you have the disease, so normal does life seem. And then just when you’re thinking you’ve beaten the disease…it’s back.

Now, even though I was in clinical remission for many months, even years, and felt much better, I have to confess that I didn’t feel completely normal. I had the joint pains that many folks taking this wonderful drug have complained about, but it was never debilitating and the pains were just intermittent. Yeah, I sometimes had to limp around for a day or two, on a sore foot or knee, and sometimes it hurt to move my wrist into certain positions, but the problem almost always took care of itself with a few days. I know lots of folks who had to take lots of drugs like Motrin or Naprosyn and such because of their pains. But that creates other problems, since the ibrutinib makes your platelets less able to clot. The Motrin-like drugs make that issue worse and can increase bleeding problems.

More seriously, I’d been having occasional heart rate irregularities, specifically one known as atrial fibrillation, usually shortened to “a.fib.” A.fib is known as an “irregularly irregular” heartbeat, wherein the heart beats with no regular rhythm at all. That’s unlike the irregular heartbeats many of us feel from time to time, when we have a few extra heart beats before our heart resumes its regular rhythm (after too much caffeine, too much stress or too little sleep). A.fib is a problem because when the heart has no regular rhythm, clots can form in the upper chamber of the heart and then travel to various parts of the body. When clots travel to the brain, they can cause a stroke. A.fib has been found to be increased in folks who are taking ibrutinib.

I got through my first couple of years on the drug before having my first episode of a.fib, but have had a half dozen episodes since then. The usual treatment for a.fib is what’s called a cardioversion, or shocking the heart back into a regular rhythm. That’s what you see on all the hospital shows where they put the paddles on someone’s chest and yell out, “Clear!” before shocking the patient. I’ve been scheduled for cardioversions in the Emergency Clinic twice, but fortunately my heart has resumed its regular rhythm on its own each time, within about eight hours, before I got to the ER early the next morning. I’m currently on a heart medication known as flecainide which helps control abnormal rhythms. We’ll see if it controls the a.fib well enough. I also take an anticoagulant medication named Xarelto when I notice that I’m in a.fib to prevent blood clots from forming.

And I’ve been tired. A lot. Many folks with CLL complain of fatigue and there seems to be more of that when on ibrutinib. But, I have denied, I think, how significantly tired I get. I don’t like to admit to weakness, so I get along the best I can and keep doing what I need to do, but there are days when I am very, very tired. There have been times I have told Kathy that I was “desperately” tired. On those days, I was having trouble keeping my head up and my eyes open. There have been days when we’ve had to cancel our activities so I can just rest. Yeah, I’ve been tired and it seems to have gotten worse in recent months. I was blaming the increased fatigue on a case of bronchitis that I’ve been fighting for months, but relapsing disease will do that too.

I’ve known for a couple of years that researchers had found that the enzyme which the ibrutinib attaches to (the BTK enzyme, Bruton’s tyrosine kinase) which helps it kill off CLL cells, can mutate so that the drug can no longer attach to it. That makes it less effective. I just didn’t know how long that might take to happen and how often it happens. In fact, I don’t even know for sure if that’s what happening to me. To tell the truth, I can’t even be sure that I’m in a relapse with certainty until a bunch of recent tests which are in progress are completed, but I know, with certainty, that my white count, which had been about 5,000 for a couple of years, went to 6,000, then 12,000, then 14,000 and now to 35,000. And 70% of the 35,000 white cells are lymphocytes and all CLL cells are lymphocytes! I had been thinking that the increased white blood cell counts were because of the bronchitis I was fighting and the steroids I’d been taking, but the steroids shouldn’t increase the lymphocyte percentage, just the bacteria-fighting neutrophil white blood cells. And that’s not good news. But it had to happen someday, I suppose.

But even if I’m truly relapsing, I have to tell you that I’ve been so pleased to have been on this wondrous drug for the past four years. At a minimum, it kept me from needing a transplant, a risky procedure which I surely would have had to endure by now if not for the excellent results of the ibrutinib treatments. And my side effects have been minimal. I have had little to complain about, and much to be thankful for.

So, now what? Well, as I have said to many of the folks who have contacted me about having CLL, we now live in something of a “Golden Age” of CLL research and treatments. When I initially got sick, way back in 2002, there was really nothing that was very good we could use to provide durable remissions. But, just then, Dr. Keating and his crew at M. D. Anderson came out with the FCR regimen, a combination of Fludara, Cytoxan and Rituxan. They achieved remarkable results with this combination therapy. In fact, some folks treated back then have STILL not relapsed and are cautiously being said to have been cured over 10-15 years since their treatments.

And now we have, not only ibrutinib, but several similar acting drugs called idelalisib, ABT-199, and now a second-generation ibrutinib-like drug named ACP-196, which is currently in trials. It’s said to be as effective as ibrutinib but with fewer side effects. And there are others in trials too. Plus, the “immune checkpoint inhibitor” drugs are now being developed. These drugs release the body’s own immune system to attack cancers of various types. These, too, have been developed at M. D. Anderson. You may have heard that former president Jimmy Carter has an aggressive skin cancer called melanoma which has spread to his brain. He is, I believe, being treated with an M. D. Anderson-developed drug called Yervoy. The last report I heard was that the tumors in the president’s brain had disappeared. That’s amazing, as melanomas are almost always rapidly lethal.

Similar drugs have been developed against lung cancers and other solid tumors. And now the researchers are ready to start treating CLL with these drugs as well. I believe that is what Dr. Keating has in mind for me, though we’ll need to talk about my various options and each option’s risk/benefit ratios.


Let me spend just a bit of time talking about the immune checkpoint inhibitors (hopefully without causing your eyes to glaze over!). I need to start by discussing our white cells. Everyone knows that our white cells protect us from infections and such. But, our white cells are made up of many different types of white blood cells, each with different functions. We have bacteria fighting neutrophils, antibody-making B lymphocytes (which can become CLL cells!), tumor suppressing T lymphocytes and several others, including NK (“natural killer”) cells, basophils, eosinophils, monocytes and more. For now, just pay attention to the T lymphocytes. These guys constantly patrol, our bodies looking for abnormal cells which may be becoming cancers or other tumors. They do this by looking for unusual proteins on the surface of these abnormal cells. But many cancers can fool the T cells by masking these abnormal proteins. They cover up, if you will, with proteins that the T cells think are normal. When this happens, the T cell leaves the abnormal cancerous cells alone and so they can spread.

But, if an immune checkpoint inhibitor is given, it prevents the cancerous cell from fooling the T cells, so the T cells can release chemicals to destroy the tumor. There’s no chemotherapy involved in this. The immune checkpoint inhibitors are just special antibodies created to block the cancer’s ability to fool the T cells. The body’s own normal T cells are then allowed to do what they’re supposed to do and they kill the tumor just as they would any other abnormal cell they come across. Pretty cool stuff!


Now, this has not been tested in leukemias, to my knowledge, but studies are underway. I may be able to be a Guinea pig yet again, just as I have for so many studies and experimental protocols over my “career” with this disease. Hey, this could be exciting.

Now, I know I may be getting a bit ahead of myself, since I don’t know with absolute certainty that I am actually relapsing, but it sure looks that way. In fact, just as I was writing this chapter, I looked up some of my new labs on the M. D. Anderson web site, and I see that my test called a beta-2-microglobulin is going up. That’s almost certainly a sign of disease progression. I’ll find out the details on our return trip to Houston in three more weeks but that’s what I’m expecting.

I am so very grateful for the world class care I’m getting in Houston. I have all the confidence in the world that they’ll do what is absolutely the best treatment for me and it will be tailored to my specific disease type as much as possible. I literally trust Dr. Keating and his crew with my life. But I also know that at some point, eventually, this disease is likely to take me down. As I said before, what CLL does is that it can come back time and time again until it becomes untreatable, even in the very best of hands. A couple of years ago a personal friend of Dr. Keating’s, who was also a co-founder of Dr. Keating’s research foundation CLL Global, died of complications of CLL after having dealt with it for over 20 years! I heard that Dr. Keating was extremely depressed after this event, as you’d expect. But the disease is going to do what it’s going to do even when being fought by the very best methods and scientists in the world.

Anyway, that’s where we are for now. Hey, this blog was getting too boring anyway!


“It is an inescapable part of the human condition that we live our lives on the knife edge of the present, forever trapped between an unchangeable past and an unknowable future.” –John Steele Gordon

Saturday, September 5, 2015

Ibrutinib; My Three and a Half Years on This Drug

Dave’s Great Adventure

Book 5, Chapter 2, Verse 11

[My apologies to anyone who has been trying to follow my story and who might have been wondering why I haven’t updated it in a while. I started to compose it (in my head) last March, actually started writing it in June, but then got distracted by some travels, some minor illnesses and, well, just being a bit lazy when it came to actually sitting down and writing. But, now I’ll get it done.]

June 2015

This story is getting pretty boring. But, that’s a good thing. Even a great thing, as that means things are going so well that there’s rarely anything to report that seems very interesting. I am way overdue in getting an update out and appending it to my on-line blog, but I just haven’t felt like there was anything of interest to report. But, now it’s been so long that I’m getting messages asking if I’m okay. And, there have been some changes, so an update is in order.

Last March of this year I celebrated two anniversaries. They were both very significant and the first was entirely the result of the second one.

The first anniversary I celebrated was that as of last March, I have been living with Chronic Lymphocytic Leukemia for 13 years! I don’t know if that sounds as incredible to you as it is to me. But when I first got sick and was diagnosed with CLL, I truly didn’t expect to live more than another 5 to 7 years or so. Many of you know that my father had the same disease and died within about five years. When he was diagnosed, back in 1976, there was no cure for the disease. And, 25 years later, when I was diagnosed, there STILL was no cure. I fully expected to be dead in a few years.

But many things have happened. I was fortunate enough, if I can use that term, to get this miserable disease at just about the time that multiple researchers were finding some more effective treatments. Not cures, mind you, but more effective treatments. Up until that time there were many good folks who advocated for not even trying to treat the disease. The feeling was that the patients would die within about 6 years, whether they were treated or not. So, the reasoning went, why torture them with treatments which aren’t going to help them live longer.

But, I was able to get a number of experimental treatments over the years that have kept me going for more than my expectations. I won’t go into the details, as they are all recounted in some excruciating detail on my blog postings, but I have been able to go from one new treatment to another, and just when it has looked like I was out of options, new options have appeared. I am one lucky guy. One of my friends in Miami says I have reminded him of a surfer who just keeps catching another wave when one runs out. Yeah, it’s really been something like that.

But that brings me to the second anniversary I celebrated in March. About four years ago I got some very, very bad news. I had been dealing with CLL for about 9 years at the time, and my treatments had been fairly successful at keeping the disease at bay for a few years at a time. That was at least in part because I had one of the more favorable chromosome types. This stuff is described in detail elsewhere in my blog, but there are at least five or more major different chromosome types among CLL patients, plus many other complex mixtures of chromosome types. I had, up until that time, a normal male chromosome type, the 46XY chromosomes. But, about four years ago I found that the disease had mutated to a different, much more deadly type called the 17p deletion (also described in detail elsewhere). With this mutation, which does not typically respond well to chemotherapy, my life expectancy was said to be 12 to 18 months, if untreated…and most treatments weren’t expected to work.

So, with my back against the wall, and with no good treatments to fall back on, I prepared for the only real option I had left, a stem cell transplant. Now, these transplants (also called bone marrow transplants) can be lifesaving and many folks are alive today only because they had such a transplant. But, and this is a big “but,” many folks have died from attempting the kind of transplant I would need. The death rate for a transplant from an unrelated donor is said to be anywhere from 25%-50% or so, depending in who you talk to. But, with no other options, I was evaluated in the transplant clinic at M. D. Anderson and signed all the papers to authorize them to start the search for a matching donor.

But, the very next day, which was in March three years ago (the other anniversary I celebrated last March), I was accepted into a clinical trial of a new drug, a drug so new that it didn’t even have a name, being called simply PCI 32765, its developmental code name. It had been tried on about 140 other very sick folks and seemed to be working very well for many of them, so I signed up to be in the trial, one of the next 40 patients to try this new stuff.. At the time, I was very sick, having large tumors in my belly, chest, under my arms and in my neck. But, within the first week of starting this new drug, which I was taking in combination with Rituxan, I could tell it was working. My swollen belly was shrinking and the lumps under my arms and on my neck were getting smaller.

And, for me, it has kept on working. I have now been on it for over three years, making me one of the patients who has taken it the longest. There are still about 90 folks out there who have been taking it for over four years now, but with every day, we’re making history, proving this stuff works and helping to find out how long it might continue to work.

It’s not a magic bullet for everyone, however. Of the 40 folks who were in my study group, within two years four had died. I don’t know if it was from disease progression (like Richter’s Transformation), bleeding or infection, or what, but 10% of my group is no longer with us.

The side effects have been, at least for me, fairly minimal. I have had intermittent but persistent pains in my joints, usually in the small joints of the hands and feet, but also sometimes in the larger joints as well; wrist, knee, hip, etc. The pains can be significant but are usually transient and last but a few days before disappearing. And I have days, many of them, when I feel significantly tired, even very, very tired. But there can be more serious problems. This drug, now called ibrutinib, and more recently approved by the FDA for general use and trade-named Imbruvica, can also cause heart rate abnormalities, most commonly a condition called atrial fibrillation, or A-fib. I have had two episodes of A-fib over the last year and a half, but both times the condition resolved on its own within less than 24 hours, so I didn’t have to be cardioverted, or “shocked” to restore a normal rhythm.

During the last two years, this medication has worked so well for me that my blood counts are near-normal, with my white blood cell count being about 5,000 at every monthly blood test (normal is about 3,000 to 10,000 or so). So, since my counts are staying normal, and because I am having, at least intermittently, a significant side effect like the A-fib, Dr. Keating has reduced my dose of ibrutinib from the usual three capsules daily, to just one capsule daily. We’ll see how my counts look after a month or so and see if I can stay on the reduced dose or whether I might need to go up to two capsules daily.

As an aside, I should mention that when this drug was first studied in the very first 140 patients, the researchers were comparing a dose of six capsules daily against a dose of three capsules daily. They found, early on, that three worked just as well as six, and caused fewer side effects, so all patients from that time on were given the lower, three capsule dose, which is what I was started on.

However, no one, to my knowledge, has done a controlled study to compare how effective one or two capsules are compared to the standard three daily capsules. I know that since the drug has become more widely available, after the FDA’s approval last year, many folks or their docs have tried reduced doses of the ibrutinib. In fact, one of my CLL “pen pals,” who was having horrible rashes with the drug, completely on his own, and not even at his doctor’s recommendation, reduced his dose to two daily and his blood counts have continued to improve over the last year, even though he had very high white blood cell count numbers when he started on the drug. Dr. Keating noted to me that he has a number of folks on reduced doses, many even as low as the one capsule daily that I am now getting.

This could be significant on many fronts. First, if this lower dose works as well as the three capsules a day, then one could expect fewer side effects with no apparent reduced efficacy. Secondly, this drug is VERY expensive. The list price for ibrutinib is $92 a capsule in the USA, or $276 daily. That’s close to $100,000 a year. If patients could be eventually maintained on just one capsule daily, that would be a significant savings for the patients and their health insurance providers.

I’m happy to have been so stable on the ibrutinib, as I truly think it has saved my life, but while I’m doing well on it, I am having some other issues. Anyone who is diagnosed with CLL is told, early on, that they are now at increased risk for a second, or more, malignancy. For men, the greatest risk is for skin and prostate cancers. Well, a couple of years ago I developed a skin cancer, a small squamous cell carcinoma of my left forearm. It was easily taken care of but now I have to get twice a year full body checkups from my dermatologist.

But, more recently, my blood test level for my PSA (prostate specific antigen) has gone up, more than double last’s number. A visit with the urologist revealed a possible small irregularity of my prostate. But, a repeat blood test a few weeks later showed that the blood test had returned to normal levels. I just had a third test and will see the urologist yet again in a couple of weeks to see where the level has gone. It looks, however, like I’m going to have to have some prostate biopsies to see if I have a prostate cancer, or to prove that I don’t. I don’t really care for the idea of the biopsies, but it probably shouldn’t be TOO big a deal. I hope.

September 2015

Okay, I’m back and I’m going to finish this up. But first I need to update the “updates,” as things have changed yet again. First, let me follow up on the prostate issue. Since I wrote all this I have had a series of prostate tests and the levels have gone down, down and down, to completely normal levels. This has happened after a couple of courses of antibiotics, so one presumes that the cause of the abnormal PSA tests was a mild prostate infection. So, no prostate biopsies yet, and I’m to get another PSA blood test next January followed by an exam. Hopefully all will still be normal.

Secondly, the trial of taking just one capsule of the ibrutinib daily didn’t last very long. After one month, my white count was up to 6,700. Now, this is a completely normal number for most folks, but my white blood cell counts had been consistently between 4,500 and 5,500 for the last two years or so on the standard, three capsules daily dose of the drug. So, the rise to 6,700 might have been significant. I reported this result to the folks at MDA and I was put on an increased dose of two capsules daily, about five weeks ago.

But, just as I was starting this new dose, I got sick with a cold which progressed to a bronchitis. I’ve been coughing for several weeks now and finally started some antibiotics when I was well past the usual viral stage of the cold but was still coughing. So, last week, when I got my next blood counts done, my white blood cell counts were up to 10,400, a major increase. Now, this is still a normal number for most normal folks, but it’s higher than I’ve been in a few years, since I started the ibrutinib. The question is, did the white count go up because my CLL is no longer well-controlled at the two capsules a day dosage, or did it go up because of the bronchitis. After a bit of discussion with the folks at MDA we decided it was most likely the result of my infection, since bacterial infections can elevate your white counts, as they go to work trying to kill off the invading bacteria and such. We’ll see if the counts are still elevated when I get my next blood test done at the end of September.

I have mentioned, in the past, about the possibility of getting a CAR-T procedure, the “chimeric antigen receptor-T cell” procedure in which one’s own T white cells are harvested and modified to fight leukemia cells. It has been used in some small studies around the country with varying success, but it’s not yet ready for prime time, I’m afraid. In fact, the MDA CAR-T tests have gone off the rails. It appears that a large pharmaceutical company hired away the lead investigator and then gave MDA a large grant, and in doing so, created a conflict of interest which MDA’s lawyers are looking into. So, for now, CAR-T is not looking like it will be an option in Houston for a while.

But other therapies are coming on strong. First, there have been a couple more oral agents approved for CLL. This gives us more and more options for treating the disease, even if one of the drugs (like ibrutinib, as an example) fails, there are others to go to, like ABT 199, now known as Venetoclax. There are several patients who have been on ABT 199 until they achieved a complete remission and then, very bravely, stopped the medicine. In at least the several months since they went off the drug, the disease has failed to return. This is amazing.

And just as exciting, I think, is the advancing of the Immune Checkpoint Inhibitors. We have known for a while that in CLL and other cancers, the body’s own immune system fails to control the disease as it should. Researchers have found that there is an inhibitor on the surface of the patient’s T white cells, the ones that normally search out and control abnormal cells like cancers, and this prevents the T cells from doing their jobs properly. But, now antibodies are being developed which block this immune inhibitor, turning the cells loose against the disease. This process has been used successfully against several solid tumors, like melanoma and renal cell cancers, and the thought is that these antibodies should work well against CLL cells as well. We shall see. I’ll probably talk about this a bit more in an upcoming message.

I want to finish up with the mention of one more anniversary I’ve had recently. Last month Kathy and I celebrated our 46th wedding anniversary. That’s another truly amazing anniversary, as when I first got sick, I really didn’t expect us to be able to celebrate our 40th anniversary together. But, now I’m doing so well, and there are so many wonderful new treatments for CLL, that I’m beginning to think I’ll be around for our 50th anniversary. This has been an important union for us, and I couldn’t have gone through all the trials of dealing with this disease without Kathy at my side. She’s been with me every step of the way and has sat by my side, hour after hour and day after day as I was getting chemotherapy and feeling sick afterwards. It’s so wonderful to have her to rely on. And, we’ve had so many wonderful friends throughout this journey who have also given us support, love and prayers all these years. We have been truly fortunate.

And this has gotten too long…again…as my stories always do. But I’ll be back when there are any changes in what’s going on and maybe I’ll be able to be just a bit more concise in my writing.


“Life must be understood backwards. But it must be lived forwards –Soren Kierkegaard

PS: If you’re the praying kind, please take a moment to remember our friend and fellow TNT Teammate and Honored Hero, Doug Campbell and his wife Stacey and their daughters, in your prayers. Doug has been in Team in Training for many years and completed many distance events with the team, raising money for the Leukemia and Lymphoma Society even while battling an aggressive, incurable lymphoma. Several years ago, when he exhausted his chemotherapy options he began looking at a stem cell transplant, but a good match could not be found. His family organized many bone marrow donor drives, which will likely help many other folks in the future, but still a good match for Doug could not be found. Finally, about four years ago, I believe, a partial match was located. It wasn’t great, but it was all that was available and Doug needed treatment desperately. So, he underwent the transplant but very soon afterwards began having significant Graft Versus Host Disease (GVHD) complications, wherein the transplanted cells attack the patient’s organs. Doug has battled valiantly for several years now, getting through one crisis after another, with Stacey ever by his side. Ironically, the transplant has cured his “incurable” lymphoma but its side effects are beating Doug up badly. Now Doug is in severe heart failure, has compromised lung functions, diabetes and more, and is not doing well. He was offered the possibility of a heart transplant, but has decided that enough is enough. He has decided to forego further treatment, having fought the good fight for so many years now. His family hopes to get him home so they can be together for what precious little time he has left. He is a wonderful guy and is deserving of your prayers and so much more. Godspeed, Doug.

Friday, November 7, 2014

My Two and a Half Years on Ibrutinib

Dave’s Great Adventure
Book 5, Chapter 2, Verse 10
November 7, 2014

I’ve been taking that near-miraculous drug, ibrutinib, for about 30 months now. I believe it has, quite literally, saved my life.

Just a little over three years ago I got very bad news. The CLL I had been fighting for nine years had mutated from a moderately aggressive form to the most aggressive form of the disease. I found that I had the dreaded 17p deletion, wherein my chromosomes had lost a gene called the “tumor suppressor” gene. Without it, the disease is very aggressive and especially resistant to chemotherapy. Most studies predict that without treatment, the expected longevity with this mutation is between 12 and 15 months or so.

The only treatment really known to work in this circumstance is a stem cell transplant (or bone marrow transplant; they are the same thing), which I knew would be a possibility at some point in my life, when nothing else was working for my disease, but I wanted to postpone a transplant for as long as possible since a transplant is not without risk. There is a fair chance of dying from the procedure, and this risk is generally quoted as being about 25% or so, depending on whom you talk to and where the procedure is done.

My doc at M. D. Anderson in Houston tried to treat my disease with a newly approved medication called Arzerra (ofatumumab) for a few months to see if it might work. But after four monthly treatments, it was clear that it wasn’t working. A CT scan showed that I had multiple tumors in my belly, chest, neck and underarms, the largest ones being about the size of oranges. It looked like it was time to see about that transplant, and so I did. I went to the transplant clinic at M. D. Anderson and was examined, filled out all the questionnaires, gave multiple tubes of blood and signed forms agreeing that I knew the cost could be upwards of a million dollars, which I would be responsible for if insurance didn’t cover it. Yikes!

But, the very next day I got wonderful news. I had been accepted into a Phase 1/2a study of a new drug, a drug so new it didn’t yet have a name. It went simply by the name PCI 32765. It had been tested recently on about 90 seriously ill folks with CLL and seemed to show great promise. I jumped at the chance to get into the study.

I began taking this drug, the first of its kind, and an orally active medication for CLL, in April 2012. My previous treatments for my disease, over the previous years, had all been IV chemotherapy, needing four to six months of therapy, several times every four weeks. But this PCI 32765 stuff…it was so easy. Three capsules in the morning and I was done each day.

When I started my treatments with the PCI 32765, it was in combination with Rituximab for the first six months. By the time I was able to start taking my first doses, the tumors in my belly had grown to be about 16 centimeters in diameter, about grapefruit sized. I looked pregnant. My belly was distended with tumor, I had large lumps in my armpits and had multiple tumors on the sides of my neck. I was very sick. But, within the first week of starting on the Rituximab and PCI 32765 combination, even before I was examined again at the clinic, I knew it was working. Within days I could tell that my belly was less distended. The tumors were shrinking that fast!

Indeed, when I had a follow-up CT scan three months after starting the ibrutinib (as the generic name of PCI 32765 came to be called) the tumors had shrunk by almost 90% of their volume. Within a year, the tumors were gone. During that time my white counts came down to normal, my red cell counts improved and my platelets stayed steady, though lower than normal, as they had been since my third round of chemotherapy in 2008.

The side effects of this near-miraculous new drug were, at least in my case, almost trivial. I had frequent pains along my joints, primarily in the small joints of the feet, hands, wrists and ankles. This was often accompanied by some redness, and the pain could be significant but almost always resolved within three or four days. Rarely did I take any medications for the pain. I also had some very minor skin rashes, a few small sores in my mouth on occasion, but not too much more. I have the fatigue that most folks with CLL seem to have, and I have all too frequent sinus infections, which are also very common, but that’s about it. Now, I know that other folks have had very serious, full-body rashes and more severe pains, some have had significant diarrhea, and some have had sloughing of their mucous membranes in the mouth and other places. But, I have been exceedingly fortunate in having so few symptoms. And, I think my experience is probably more typical than that of those folks who have had worse problems with side effects. In any case, the side effects are significantly less than could be expected of a bone marrow transplant. This is one amazing drug.

But, it’s not perfect. As I’ve mentioned, there is a small failure rate for some of us on this drug, mostly among the people like me with the bad mutation, the 17p deletion. But, I’ve been told it’s only about a 5% failure rate, with a few other failures occurring in the 11q deletion patients and a few others as well. Apparently some folks have developed a more serious form of our disease, with Richter’s transformation, where our disease transforms into the much worse “diffuse large B cell lymphoma” (DLBCL). So, ibrutinib is not a perfect drug, but nothing is when you’re treating cancers of any kind. But, man, is it good. I’ve been in contact with many folks all over the world and all of them who have started taking ibrutinib, except one unfortunate guy who developed DLBCL, are doing just great.

Initially, when starting the Rituximab and PCI 32765 treatments, we were going to Houston weekly. After five consecutive weeks, the frequency was reduced to monthly for the next five months. As my exams and labs began to normalize, the appointments went to every three months, then every four months…and at my last visit in August, after my two and a half years on ibrutinib, they told me to go away and not to bother them again for SIX months, sending me off with a supply of ibrutinib worth more than the car I was driving! I continue to take three capsules daily and the list price per capsule, now that it has been approved by the FDA, is about $92 each. So, six months’ worth of capsules is indeed worth a fair amount.

Kathy and I have been taking advantage of my/our good fortune and, after this excellent news, went on a 16 day river cruise in Europe, passing through Germany, Holland, Austria, Slovakia and Hungary. This was a very, very nice cruise and, despite having lived in Germany for seven yeas while I was in the Army, we saw many cities and places we hadn’t visited earlier in our lives. And, life for us has returned pretty much to normal again. The only continuing problems I have are the intermittent joint pains and the enduring fatigue. But, those are very small prices to pay for having access to this incredible new drug.

The standard three capsule daily dose is something several folks have been looking at. When this drug went through Phase 1 and Phase 2a studies, the only doses studied were 840mg and 420 mgs daily (six or three capsules a day). It was quickly found the three capsules work as well as six, so the larger dose was dropped. But, to my knowledge, no one yet has studied any lower doses. Doc Keating has mentioned wanting to study the efficacy of lower doses, and to study leukemia cell receptor saturations at lower doses, but the drug was controlled by the company and human use studies are exceptionally difficult to get approved. As they should be.

But now that the drug has been FDA approved, is widely available and can be prescribed by any physician, I know that there are people who are trying lower doses. I have a correspondent who, on his own, lowered his dose from three capsules daily to two because he was having horrible full-body rashes. His rashes have improved and, in the short term, his blood counts seem to be continuing to improve. And I have heard of another patient who was refusing any chemotherapy of any kind, who was convinced to try just one ibrutinib daily, and also in the short term, I hear that she is improving. Time will tell what the optimal dose will be. I keep expecting to hear of a clinical trial with one, two and three capsules a day, to see if they are, or are not, equally effective.

Meanwhile, the FDA has approved yet another oral drug, idelalisib, for use in CLL. And there are more in the pipeline. The stuff called ABT 199 is showing great promise and should be coming along soon. It’s the drug that Doc Keating said I may be switched to if I relapse while on the ibrutinib.

But, even as these first generation drugs are being developed and approved, there is now a second generation drug like ibrutinib (another BTK [Bruton’s tyrosine kinase] inhibitor) in trials. This drug is called ACP 196 and it is in Phase 1 trials in multiple centers right now, including at M. D. Anderson.

In other recent notes about this wonderful drug, I have recently heard news that makes it much more convenient to take. Originally we were given strict instructions to take it on an empty stomach, at least thirty minute before we ate, or two hours afterwards. But recently one of the researchers has said that the absorption is the same with or without food in your stomach. It just seems that there is less diarrhea when taken on an empty stomach. Since I’ve never had any issues with that at all, I now just take my capsules in the morning with breakfast. And, I’ve mentioned the CARs procedures in previous messages, where one’s T lymphocytes are modified to attack your leukemia cells. The folks at M. D. Anderson have been working on a specific type of CARs (or also called CART) called the ROR1 CARs. But, as of my last visit, it still hadn’t gotten into clinical trials, so I don’t think that possibility will be in my future any time soon. But, work on this is slowly progressing.

When I started this series of little stories, they went out solely to family and close friends, and though I had a fairly long mailing list, it was limited to about 150 folks. But, just a few years ago our kids convinced me to publish my messages in an on-line blog form, to make them easier for my friends and family to access. And this has had an interesting unintended effect! Other folks around the English speaking world, when Googling “ibrutinib” or “CLL” and other topics, have stumbled upon my stories and I have had contact with many other people with this disease, or the family members of folks with CLL. I have correspondents in England, Canada, Australia and across the USA. My stories have been read, on-line, by hundreds and hundreds of people. I know this because Google, who runs the blog site, keeps track of every click on my stories.

It has been a wonderful thing to share our stories with each other and to be able to commiserate when we had to. I have shared my experiences with lots of folks and have tried to judiciously dispense advice about what might be available and/or advisable for others with this disease. But, I’ve had to put a disclaimer at the top of my blog, noting that I’m really not an expert. I know, or at least I think I know, a lot about CLL as I’ve been dealing with it, reading about it and writing about it for almost 13 years now. But, I have to tell you, when I start talking with Dr. Keating about the details of CLL, or when I get into the research articles about CLL that are published in the hematology/oncology journals…I admit that I have trouble understanding a lot of it. And so, I can fully appreciate how non-medical folks would have difficulty comprehending so many of the details of this very complex disease. So I am very happy to try to help other folks understand what they are facing and what their options are. It is nice to be able to tell them now, after many years of having little real hope, that we live in a “golden era” for patients with CLL. There are now so many very effective and non-toxic options for us. Most of us shouldn’t have to have harsh chemotherapy and most of us should be able to avoid a stem cell transplant and its attendant risks. A cure is surely coming soon.

And, so, that’s all for this episode. I’ll be going back to Houston to be examined and have another bone marrow biopsy in January. My monthly labs tests done here at home have been completely stable and so I’m fully expecting that my check-up in January will be normal as well. If so, I’ll probably be continuing on the ibrutinib, as long as it keeps me disease-free. The manufacturer has agreed to keep its early test subjects supplied with the drug as long as we are willing to be examined periodically, as they need long-term data about its effectiveness and side effects. So far, we only have about four years’ worth of data on a few hundred patients. It’ll be nice when we have, maybe, ten years or more of data to show that it keeps on working for many, many years.

Here’s hoping!


“Take therefore no thought for the morrow; for the morrow shall take thought for the things of itself. Sufficient unto the day is the evil thereof.” Matthew 6:34

“I have told you these things, so that in me you may have peace. In this world you will have trouble. But take heart! I have overcome the world. ” John 16:33

Tuesday, July 8, 2014

About that transplant...

Dave’s Great Adventure
Book 5, Chapter 2, Verse 8
July 7, 2014

Dr. Keating came into the exam room and sat down. Then he leaned a bit toward me and smiled the impish smile he often has when we’re talking. “Don’t worry about those terrorists over in the Transplant Clinic,” he said, with his Australian accent.

I had expected to have to make a major decision about a transplant soon, probably at my visit in May. I even had an appointment to see the very kind folks at the Transplant Clinic which had been on my schedule for three months. Each time we get to M. D. Anderson on the morning of my appointments, I always ask for a printout of those appointments to make sure none of the times has changed. But this morning when I got the printout of my appointments and times, the appointment at the Transplant Clinic had disappeared. I was surprised.

So, I got my blood drawn as scheduled and then went to the Leukemia Clinic to await my appointment there. I saw Jackie, as I usually do, and she went over my history and did the usual physical exam. All was well. My labs tests were all stable and my white and red blood cell counts were normal. No evidence of relapsing disease. I told her that I was puzzled about the missing appointment at the Transplant Clinic, as I had expected to be talking about the possibility of a transplant in the fairly near future.

So Jackie completed her exams and questions and left the room, leaving me to await Dr. Keating’s time with me. And that’s when he came in and told me that a transplant wasn’t very likely in my immediate future.

Things are going too well, he said, to think about doing a transplant right now. My marrow seems devoid of disease and my labs and exams are all normal. So, with that subject off the table, I asked some questions I had, questions which had been lingering in my mind, bothering me about what might lie ahead. I had been especially worried about the problem of folks like me with the 17p deletion failing the Imbruvica therapy. I asked, what percentage of us are failing the therapy so far. I had been told only that it was “common” in the past, but had no idea what the magnitude of the failures might be. What was it, I wondered; 80% of us, 50%, what? No, he said, it’s more like 10%, which I found reassuring because, I’m sure (as we all are, of course) that I won’t be in that 10% group. So then I asked, of those who 17p deletion patients who have failed, how many have died. Well, none of them. They are getting treated with various other therapies; some with ABT 199 (another drug in the Imbruvica category), Arzerra (similar to Rituxan but more “humanized”) and other things. Probably some have had transplants, too, but I failed to ask about that. And that I found to be very reassuring. I also asked about how the disease came back when folks relapsed, as I had wondered if it came back as Richter’s or worse. Yes, it does some times, but that apparently is not seen routinely. So, it seems like there is still a lot of good news about this drug and my continued treatment with it.

We moved on to talk about the CARs (chimeric antigen receptors) studies being done at MDA. I have mentioned this new procedure in some of my previous stories, but I’ll touch on it again just briefly…if I can actually be brief! This is the procedure wherein one’s T-lymphocyte white cells are harvested, much like donating blood or platelets and such. But then the patient’s T-lymphs are treated with a modified retrovirus, like an HIV virus, to insert a gene into the DNA of the patient’s lymphs. This gene will do a couple of things. First, and most importantly, the T-lymphs will be modified to search out cells with a specific protein on their cell membranes. All CLL leukemia cells have a protein called CD19 on them and the early studies of CARs have looked at teaching the T-lymphs to kill cells carrying this protein. The second thing that the T-lymphocyte white cells are taught to do is to reproduce when they find and kill such a cell. There have been some notable successes with this approach, including a very few folks who are now, apparently, cured of their disease. But, there is a problem with this approach. Although all CLL white cells carry the CD19 protein, so do all normal B-lymphocyte white cells, and they are the cells that ultimately make your antibodies so you can fight off infections. So, although a few folks have been cured of their disease, they must frequently get infusions of antibodies, gamma globulin infusions, since they can’t make their own antibodies.

The folks at MDA are taking a different approach. One of their colleagues in Sweden discovered a protein on CLL cells called the ROR1 protein. This protein is generally found only on certain malignant cells and a few immature cells. It is not found on normal B lymphocytes. So, if one’s T-lymphs could be modified to search out and kill only cells with the ROR1 antigen, then the problem of the normal B-lymphs getting caught in the crossfire might be solved, along with the problem of not making one’s own antibodies. By the way, ROR1 is also found on kidney, breast, lung and colon cancers, so this could possibly have applications beyond the treatment of CLL.

But there are folks who say they’ve found the ROR1 antigen on other tissues like fat cells, pancreatic cells and such. If that’s correct, and the ROR1 protein is found on these tissues in significant quantities, then it might not be good for the patient. Even if you think it would be okay for your T-lymphs to gobble up your fat cells, the problem could be that they would destroy massive amounts of the cells and the cellular debris could clog up your kidneys, causing “tumor lysis syndrome.” That’s not good at all, and can be deadly. But this problem, if it exits at all, does not seem to be a serious issue in the early going. So, the researchers at MDA have started this process with a very few patients so far. I really don’t know if we’re talking about one or two folks, or if they’ve tried it on six or eight. I just know it’s not many yet. That’s for a couple of reasons.

First, just doing this is very labor intensive, as you can only make one batch of cells for any given patient. My cells, for example, wouldn’t work for anyone else. These things can’t be mass produced in large quantities. So each patient will have his or her own personalized batch of T-lymphs made up for them.

The next reason it’s going slowly, is that it’s a very new process, and as with most very new medical processes, it’s generally tried out first on the folks who are the sickest and have no other options. Therefore, folks like me, who are currently doing well on the Imbruvica, are not really great candidates for a process which has not yet been proven to be effective. So, we’ll see how it goes with the early studies and will hope to see great results without too many complications. If things go well in the study, I may be a candidate somewhere down the road as data is collected on the pioneers of this procedure. Doc Keating says I don’t want to be the first candidate for this new procedure, but that he’ll let me know when they’ve done ten or so with good outcomes!

By the way, all this research on the ROR1 CARs is being done in conjunction with the Transplant Clinic folks, so it’s possible that they are in on the plan to eventually try to get me into the study, and that may be why my appointment with them at my last trip to Houston mysteriously disappeared.

While we’re talking about ROR1, let me also mention that other researchers are working on creating ROR1 antibodies which can be given by injection/infusion to attack CLL cells. This would be very much like the Rituxan I’ve had several times, but would not (like the Rituxan does) affect normal B lymphs cells along with the bad guys. This would have to be given repetitively, like Rituxan, and would not be a cure, as the antibodies would eventually disappear from the patient’s circulation. The advantage of the ROR1 CARs therapy is that it could, in theory, be a cure if the ROR1 treated cells persist indefinitely, continuously seeking out and killing CLL cells wherever they find them. Cool stuff!

So that’s where we are right now. I’ll continue to take the ibrutinib/Imbruvica for the foreseeable future, as long as it keeps working for me and as long as my disease doesn’t find a way around its effects. And we’ll keep an eye on the research being done on the ROR1 CARs procedure, to see if I might ultimately be a candidate.

Until the next time, after my visit to Houston in August.


“Work for a cause,
Not for applause.”