Sunday, January 29, 2017
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
Book Seven--The Transplant, starting in January 2017
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 email@example.com
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 15 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!
Saturday, January 28, 2017
Wednesday, November 2, 2016
Book 6, Chapter 1, Verse 5
noun: dilemma 1. a situation in which a difficult choice has to be made between two or more alternatives, especially equally undesirable ones (Oxford Dictionaries) 2. a choice between a stem cell transplant which may kill me with graft versus host disease or staying on the venetoclax which may cause my death by Richter’s Transformation. (Dave Eckberg)
Man, the venetoclax is working great. Even spectacularly great! I’ve now been on it for about 22 weeks and everything is going the right direction. It’s causing me few side effects, my lab tests are normalizing and a recent CT scan showed that my enlarged lymph nodes are shrinking. This is one amazing drug.
Maybe even astounding. Recent follow-up labs on my bone marrow biopsy from a few weeks back show that the percent of leukemia cells in my marrow has dropped from 93% in late May, 2016, to only 0.6% in late August! That’s not a misprint. From 93% to less than one percent leukemia cells in just twelve weeks. That’s just astonishing and it’s more than I could ever have hoped for. I’m doing great!
And that’s why they want me to do a stem cell/bone marrow transplant (they are the same thing) now. As I mentioned at some length in my last story, it’s when you’re doing wonderfully well that they rain on your parade and say, “Okay, it’s time for the transplant.” Of course, they pick this time when you have a reduced disease burden and are feeling well because that’s when a transplant is most likely to “take” and possibly cure your disease.
I’ve been fretting and worrying and stressing and agonizing over having to make this decision for many weeks and months. I knew the time would come when I would have to cross this bridge. I have never wanted to have to do a stem cell transplant, but I have always known it would be my ultimate safety net when nothing else was working. And now, I’m about there. And here’s why.
I have written out long lists of pros and cons for each of my options, which are whether to go for the transplant or to continue on the venetoclax which is doing so well for me. I have drawn out algorithms and decision trees for both. I have asked questions, looked at on-line data, and I have looked over recent data from M. D. Anderson about their success rates after transplants. And here’s what it looks like.
The results, in very general terms, for a “matched unrelated donor” stem cell transplant are divided into quarters. About one quarter of the patients will die. About one quarter will fail to engraft and/or relapse. About one quarter will survive but suffer from significant graft versus host disease. And about one quarter will be cured. These are very general outcomes, but approximately reflect one’s possible outcomes after transplant. I’ll get back to this stuff in a moment.
Now, if I stay on the venetoclax, what are my likely outcomes? Well, to start with, I WILL relapse at some point. That likelihood apparently approaches 100%. We just don’t know when it will happen. As I mentioned previously, the average progression free survival is said to be 16-24 months, depending on whose study you read. But that doesn’t mean I can safely wait this stuff out for 16 months. The relapses start early in some folks and there is a slow downward trend in survival rates from early on in the studies. I could potentially relapse at any time…or I might not relapse for a couple of years!
And if/when I relapse, current data says I’ll have a 50% chance of coming down with Richter’s Transformation, which I mentioned in my last story. Richter’s is very bad news. For someone like me, with a history of several failed courses of chemotherapy and the 17p deletion, Richter’s for me pretty much means “game over.” Sometimes one can attempt to treat it with a stem cell transplant, but then I’m back to that same decision again, but in far worse shape. Plus, the chemotherapy I’d need before that transplant likely wouldn’t work for me since my disease has worked its way around chemotherapy several times in the past.
But what if I relapse and don’t come down with Richter’s? Indeed, what? Well, there are several, or even many possible options, but all are unproven. If I could get into a CAR-T study (chimeric antigen receptor-T cell) that might hold out the possibility of a cure, but the success rate is still low, and there are deaths involved in these studies as well, plus lots of failed procedures and relapses.
So, more drugs? There is nothing left for me that is known to work. We have talked about trying a combination of Revlimid and obinutuzumab which should, in theory, work. And it might work well. But it’s no more likely to cure me or give me a prolonged remission than any other combination I’ve been on. And when I relapse on it, then what? Once again, I’m back to the same question of, what now? And a transplant would seem to be my best option once again, but I’d be older and probably sicker than I am right now.
“When you come to a fork in the road, take it.”—Yogi Berra
I stalked Dr. Keating at our last visit to M. D. Anderson. I didn’t have an appointment with him and didn’t even know for sure he was in the clinic that day, but I wanted to talk to him about a transplant, since he had been my doc for ten years. He’s now not permitted to be involved in my care, at least directly, as he didn’t take some mandatory “class” instructing docs how to safely administer venetoclax. The class was put on by AbbVie, the manufacturer of venetoclax, since some patients had been killed by giving the drug too rapidly in early studies (see “Ramping Up The Venetoclax,” which I wrote recently, for more details about this). I’m sure it was a lawyer’s “cover your ass” kinda thing for the manufacturer, as they didn’t want to be involved in a lot of lawsuits which would inevitably follow the death of a patient taking the drug.
I had been leaning towards a transplant for a while, since it seemed like I was pretty much out of good options, but I wanted to run it past Doc Keating. He’s been my “security blanket” for many years and I wanted his opinion. Sitting in the waiting room, hoping for evidence that he was, in fact, in the house, I finally heard his voice and knew he was there (yeah, I heard him before I saw him!). I asked one of the staff if they could get a message to him asking if I could take five minutes of his time at the end of his morning clinic. Then I waited to see if he would talk with me. The clinic was ostensibly finished at noon, and no one came out to invite me in to the exam rooms. I waited a while longer, and longer. Then, at 12:45, Alice, the nurse practitioner came to the door and hustled me into the clinic. Shortly, Doc Keating kindly joined Kathy and me and gave us both his famous hugs.
I told him why I was there and mentioned that I was disappointed that I hadn’t been able to see him in many months because of the venetoclax thing. He smiled, a wry smile, looked down and then back up at me. He said, shaking his head slowly, “I’m on the board of advisors for AbbVie…and I can’t give…their… (insert a pejorative adjective here if you want to; he didn’t, but I imagined it)…drug?” he asked rhetorically.
But we talked things over and went over the data that is available about the venetoclax and transplants. He discussed my overall outlook and possibilities, options and likely outcomes and finally said (very Nike like) “Just do it.” So, I am.
And it boils down to this; if I stay on the venetoclax I have a 50% chance of Richter’s in the reasonably near future, which is saying I have a 50% risk of dying within the next year or two or three. If I get the transplant I have about a 25% risk of dying from the immediate or longer term complications.
I’ve been to the transplant clinic again and met with Dr. Khouri, who has been doing these for many, many years. He presented me with some new information about a new “conditioning” regimen (conditioning is pre-transplant chemotherapy) which is yielding better overall results and lowered morbidity and mortality. We said we were going to do it, and so the wheels are in motion.
I’ll have much more to tell you about the transplant data later, but basically the new regimen has reduced the immediate death rate to (“only”) about 10% or so, with reduced “graft versus host disease.” But that’s a whole new topic, for another story.
One last thing; my potential donor is an altruistic 41 year old Swedish woman with A+ blood type. That’s all I will know. And at this point she knows only that someone in the USA is interested in some of her stem cells, and she is willing to part with some in hopes of saving the life of a complete stranger. She will get nothing for her troubles other than the knowledge that she may be doing something wonderful for this stranger. She may save a life. And you could too. By signing up with “Be The Match” ( www.bethematch.org ) you can be painlessly screened, with a swab of your cheek, to be a potential stem cell donor and have the incredible opportunity to save someone’s life. Donating stem cells is generally very similar to giving blood, the stem cells being collected with IVs in each arm, so don’t be fearful of a painful experience, okay? I know you’ve heard stories….
And that’s all at this point. We’ll be going back to Houston next week for more preliminary testing. As I’ve drolly said to Kathy many times during the course of this disease, “This could get pretty exciting.” But truly, it’s not exciting. It’s scary and I’m really scared.
“Through many dangers, toils and snares,
I have already come;
‘Tis grace hath brought me safe thus far,
And grace will lead me home.”
--“Amazing Grace” by John Newton
Saturday, September 17, 2016
September 17, 2016
Last month Kathy and I went to Houston to celebrate our anniversary. It was our 47th wedding anniversary and we wanted to have a special time. We had a safe trip down to Houston and checked into our hotel. I had planned a nice night out, an evening meal at Buon Appitito which is a really cute little Sicilian Italian restaurant, in an old converted house, just west of the medical center on Holcombe. It’s perhaps a mile or so down the road. It’s really nice. I lined up a small room in the back and even had the owner arrange for his musician to come in to play some romantic musi
No, no, no! Hell no! That’s not the way it was. That’s the way it should have been, that’s the fantasy we all have of a perfect night out with our wife, on a special day. But no. We were in Houston because I have CLL, an incurable, lethal disease that we’ve been dealing with for almost 15 years now. We had to be in Houston on our anniversary, but not for the anniversary. The anniversary was just coincident to our visit. The purpose of our trip, the lab tests, a bone marrow biopsy, CT scans and more, overshadowed our special day. It did it again. Over the years, the disease has stepped on and caused us to miss family reunions, funerals, birthdays, Father’s Day gatherings and a whole lot more. It has, on many, many occasions, taken control of our lives and our schedule to the point that we have to plan our lives around it. Cancer sucks!
And Kathy was sick on our anniversary and couldn’t leave the hotel room anyway. Happy anniversary, indeed.
And so it was that on our “special day,” August 23rd, I was wandering the halls and passages of M. D. Anderson alone. For the first time ever. Kathy has always been at my side, for fifteen years; at every visit, lab test, CT scan, infusion or whatever, until that very day, our anniversary.
I showed up at the clinic, Leukemia Clinic East, to check in a little early, about 9AM to get blood drawn. I had to get blood drawn before I could eat, and I had to eat before I could take my venetoclax. But immediately I had to skirmish with the still-new and still-confusing (after six months in service) electronic records system, which is officially known as EPIC. Maybe more like epic-fail, I often think. I checked in and got the requisite white plastic band applied to my wrist, which has all my patient information, bar codes and the like on it. You can’t get anything done without it anymore. Next I needed to get my vital signs done (blood pressure, pulse, weight, temperature and such). Should be an easy thing, right? I got in a short line and waited a few minutes to get to the front of the line. But just then, the system was “down.” Three staff clustered around the terminal trying to make it responsive. No luck. We were told to take a seat, told that we’d be called up for our turn at the “vitals station” soon.
I waited. The lab folks were looking for me and finally got tired of waiting on the vital signs and just took me back to the lab to get the blood drawn. Exiting the lab I saw that the computer at the vitals desk was still down so I took a seat again. But now I could at least eat and take my venetoclax. Eventually a few people were called up from time to time, but not me. An hour went by and I had an appointment for a bone marrow biopsy at 10:30. So I left without having my “vitals” taken. That’s generally a cardinal sin and can prevent you from getting anything else done until you get in the correct line and get all the blanks on your electronic chart filled in.
I got to the bone marrow biopsy clinic on time and found that they were right on schedule. In fact, they were waiting for me. Seems they had folks showing up late. Problems with vital signs, they told me! The biopsy was quick and easy. I had the drill used on me for the first time and it made the procedure even quicker than it usually is. It sounds a bit like a dentist’s drill and the thought of having a drill going into your hip is not pleasant, but was incredibly quick, easy and the drill part was totally painless. The whole thing was over in four or five minutes.
Bone marrow biopsies have a horrible reputation. Everyone “knows” that they hurt more than anything--absolutely anything--else. But, I can tell you that at M. D. Anderson, they aren’t a big deal. When I had them done in Denver, years ago, they WERE a big deal, and they were, in fact, excruciating. But the folks at M. D. Anderson are really good. Most docs in community oncology clinics do, maybe, a couple of biopsies a month, and so they aren’t all that skilled at them. The folks doing the biopsies in Houston aren’t docs, but they do up to 20 a day. And they are really, really good at what they do. I still don’t like having them done, but they simply don’t hurt any more than a flu shot or maybe falling down and skinning your knee. The worst part for me is the worry that the procedure WILL hurt like the ones I had years ago in Denver, so I tense up, but they never, ever hurt like my first ones.
By now it was about 11AM. My next appointment wasn’t until 1PM, so I decided to get a quick lunch. Since I was a bachelor for the moment, I had a bachelor kinda lunch; a cup of yogurt I had in my backpack and a bag of peanuts and a diet Coke I got from a machine. Simple and easy. I sat alone on a bench in the skywalk between the main building and the Rotary House to eat my lunch and just watched folks from all over the world walk by.
At 12:30 I decided to go back to the Leukemia Clinic and see about getting my vital signs taken as I had a 1:00 appointment with Doc Thompson. I approached the vital signs cubical and sat down. The nurse asked what she could do for me and I said I needed my vital signs taken. She told me I’d have to check in first. I told her I had. She checked the EPIC system which told her that I had not checked in yet. Showing her my official M. D. Anderson certified wristband, I assured her I had. She looked at it, scanned it, and checked the computer which still said I hadn’t checked in. It said I had checked into the lab but not the clinic. Now, understand that the research lab, which is where I had my labs drawn earlier that day, is within the clinic, feet from the exam rooms. And that the desk at which I had checked in earlier that day was only about six feet from where I was sitting, waiting to have my vitals taken. Yet I had to be checked in again. Common sense and a paper chart wouldn’t require such jumping through hoops simply to get a blood pressure taken. But the computer system requires that all the appropriate boxes be checked off in the appropriate but illogical (to me) and probably unnecessary sequence.
My visit with Doc Thompson went very well, once he was able to get to me. He was very, very busy that afternoon and kept being called out to consult with other docs and nurses, and to take consults on the phone. But once we got to talk and he was able to examine me, all was great. My labs have gotten closer to normal than they’ve been in a while, the preliminary smear from the bone marrow biopsy was already back and was approaching normal (the percentage of lymphocytes in the marrow had dropped from 50% to 20%) and on exam, he could find no palpable, enlarged nodes. And this was after only 12 weeks of venetoclax.
We talked about my options. He pushed harder on a transplant, wanting it seemingly sooner rather than later. He said he’d get in touch with the transplanters and give them a heads up about me. And he said he was going to present my case at grand rounds, so that the whole collective brain-power of the leukemia team at M. D. Anderson could weigh in on my treatment. I think I’ll be a high risk patient, for many reasons; my age (I’ll be 70 later this month), my many previous treatments, my 17p status (I suppose it makes it more risky), and so on. But, despite my great response to venetoclax, he wants me to get going with the process of preparing for a transplant.
And here’s why:
The early data on folks like me (and now I’m talking specifically about patients heavily pretreated with multiple relapses in the past and who are refractory to or who have failed either ibrutinib or idelalisib) show that about 70-80% of us will respond to venetoclax. That’s up from the 60% which was reported just last December. But the average “progression free survival,” for those of us who respond while taking venetoclax, is somewhere between 16 and 24 months, depending on who you talk to. These numbers are in flux as the data is being generated even as we’re taking the stuff. We are the folks whose survival is being measured to create these numbers.
And, about half of us who relapse on venetoclax will do so with a Richter’s Transformation. That’s a big deal. Richter’s is bad, very bad. It’s a very aggressive lymphoma. Another Dave with CLL, who had a very well-written blog called CLL Diary (www.clldiary.blogspot.com) developed Richter’s. He said comparing Richter’s to CLL was like comparing Godzilla to Bambi. That was one of his last blog entries before he died.
So, it would appear that a relapse is all but certain for us and if we wait to relapse, much worse things can happen. And, remember, that if you are to ever have a transplant, your best shot at a successful procedure would be to do it when you’re in a deep remission. Yeah, just when you’re doing wonderfully well and feeling great, they want you to risk your life on a transplant. Most of us CLL patients will need “matched unrelated donor” stem cells (inelegantly called “MUD” transplants) unless we have a sibling who matches our marrow. Any one sibling has a 1 out of 4 chance of matching you. I have four siblings but none of them match me! But, with a MUD transplant, the death rate is routinely said to be about 25%, last time I looked (some say it’s as much as 50%). That number seems not to have budged in 15 years, as that’s what I was told back in 2002 when I first was diagnosed and we were testing my siblings, who didn’t have the common decency to match me! (Insert smiley face emoji here!)
And so my options right now are to consider riding out the venetoclax as long as it keeps working and hope nothing worse happens to me in the meanwhile, or getting into a deep remission with it and then rolling the dice on a transplant. There really is nothing else out there that is proven. Yes, CAR-T cells might work, but right now the success rate is about 20% or so. Maybe try Revlimid (a thalidomide derivative) and obinutuzumab (another anti-CLL antibody which is more powerful than rituximab) to see what happens, or something else. And there are a host of yet unproven new small molecule inhibitors in the pipeline, like IPI-145, TGR-1202, ONO-4059 and ACP-196. But, of all the possibilities out there, nothing looks any better than a transplant for me, in my situation right now. Remember also that a transplant is the only proven cure for this disease. Yes, there are some lucky IGHV mutated folks out there who have been in extended remissions after getting FCR, and some of these are cautiously said to be “cured,” but they are the exception and not the rule.
And that brings up another issue. Should I have just gone for the transplant when I was in remission from the ibrutinib? I was seeing the transplanters back then and they were pushing hard to get me to have a transplant while I was in a good clinical remission. They had some possible donors identified and I had signed all the papers, gone to all the classes and everything. But, I didn’t want it. I didn’t say it exactly this way, but I kinda told them, “Are you crazy! I’m doing GREAT on the ibrutinib!” But, as Doc Thompson said to me recently, “Yeah, you were doing great until you weren’t.”
And, as great a drug as venetoclax is, it doesn’t successfully treat all the folks like me who relapse on ibrutinib. Since the current data seems to show that 70 to 80% of us will respond to venetoclax, that leaves somewhere between 20 to 30% of us who will not respond to venetoclax after relapsing on ibrutinib. Those folks would then have no other really good options (at least at present, since nothing better seems to be coming down the pipeline right now). So, should 17p deleted folks who are in clinical remission on ibrutinib just bail out and go for the transplant, knowing that they may not be saved by venetoclax if/when they relapse? Tough question. Again, it gets asked just as you’re feeling and doing great on the new wonder drug, the ibrutinib. But, when you’re in remission, your odds of a successful transplant are the highest. I didn’t seriously consider a transplant when I was on ibrutinib because, well…I thought I’d never relapse. But I did. If I’d had a transplant four years ago I would have been younger and, in theory, at a lower risk.
But there are never any easy answers or absolutely correct answers when deciding what to do with your CLL. There are just lots and lots of options. “The only true wisdom is knowing you know nothing,” said Socrates. I used to think I understood this disease but the more I learn about it, the more I realize I really don’t know very much at all.
We’re going back to Houston next week. I have appointments with Doc Thompson and the lab, as per usual. But, Doc Thompson was true to his word and has called the transplanters to let them know we’re again thinking about doing one. They then called us a few weeks ago and set up an appointment with my transplant doc, Dr. Khouri, one of the pioneers in the procedure. I’ll be seeing him and his team on Wednesday. But, the nurse who called us let us know some interesting information.
I was close to getting a transplant four or so years ago, just before I started on the ibrutinib. At that time they did all the typing of my cell lines in preparation for looking for a matched donor for me. Well, they still have all that data on file. The nurse had taken the liberty of looking at the current lists of possible donors registered in donor banks around the world and found a possible 10 out of 10 match for me! This is not a certain match, as more studies need to be done, but she has already asked for some follow-up labs to be done on this person. Now, even more interesting to me is the fact that this possible donor lives in Europe. That makes a lot of sense, since my genetic heritage is 50% Swedish, about 25% German and the other 25% is almost all English, Irish and Scottish, with a trace of French Huguenot tossed into the mix.
So, next week we start looking at my possibilities and will start trying to decide what might be the best time to get on with the transplant. I still do not want to do this, but it looks inevitable. I’ll see what Doc Thompson has to say and hear what he found out at the “grand rounds” at which he is supposed to have presented my case. I will literally have to trust him and the other M. D. Anderson docs with my life. Just like so many other folks have for years and years.
The day after my meeting with Doc Thompson I had another CT scan done; abdomen, chest, head and neck, the whole thing. I have had a chance to look at the report on-line and the reports are good. All my enlarged lymph nodes are shrinking rapidly. That and the normalizing blood counts make it look like I might soon be in a great remission. At which time, I will need to make a decision.
A couple more short topics before I close. If you’ve read my stories for a while you know that I have been seeing Dr. Keating for a decade or more. Yet I haven’t mentioned his name at all in connection with my venetoclax trial. And I can’t be sure, but from the asides and looks on folks’ faces when I ask the question about why he isn’t in the study, it sounds like he didn’t take the “class” AbbVie requires of all docs who use venetoclax. And it sounds like he probably skipped it willfully. I infer that he flipped them a metaphorical middle finger and probably said something to the effect that “I don’t need to take your effin’ class to give this drug. I’ve been treating CLL for decades and am a world renowned clinician and teacher.” Understand that these are my imagined words and in no way constitute a quote. But it’s interesting that one of the most famous CLL docs at MDA is not allowed to have his fingerprints on the study.
And one other thing; a few weeks ago I wrote up a little tutorial about what lab tests meant in terms of a white blood cell count of 1,000, or 100,000 or whatever. I was reading over my story again last week and realized that I have my units wrong! Probably there will not be one person in a hundred who will care, but I want to point out that my numbers were off. Just a bit. By a factor of 1,000! The blood counts I referenced are the number of cells in a microliter (or one millionth of a liter) and not in a milliliter (which is one thousandth of a liter). So, if you multiply all the numbers I was proudly showing off with by 1,000, you will have correct numbers. So the five billion white cells I was mentioning actually should be five trillion cells. And the same for all the other totals mentioned…just multiply by 1,000. If anyone really cares.
“The future ain’t what it used to be.”—Yogi Berra
Saturday, September 10, 2016
I want to take a moment from telling my little stories to touch on something that’s very dear to my heart and important to the lives of many people across the world. That’s the topic above; Supporting Leukemia Research.
In my “career” with this disease, which is now approaching fifteen years, I have intersected with leukemia research many times and in many forms. I’ve been a beneficiary of its results, I’ve been a participant in the studies of new drugs and new combinations of drugs and I’ve actively supported the research efforts by making personal donations and by raising funds to help major institutions further the studies of better ways to combat our diseases.
When I first fell ill, in the spring of 2002, I was extremely disappointed to find that there really wasn’t much out there that was very good for CLL. My dad had died of CLL 25 years previously, and I found very quickly that despite a quarter century of study, there still were no really good treatments available. The best thing going was a combination of fludarabine (Fludara) and cyclophosphamide (Cytoxan). But this combination was, in many ways, like taking Tylenol for pneumonia; the drugs lowered your white count and made it look like you were doing better (much like Tylenol would lower your fever and make you feel better if you had pneumonia) but they really didn’t do anything about the disease. It always came back!
But that very year, my doc in Denver where I lived at the time, read an article about Dr. Keating’s new groundbreaking research into using the Fludara and Cytoxan in combination with a newer drug, rituximab, which was not yet even approved for CLL. He reported incredible results with amazing rates of complete remission, rates never seen before. And many of the remissions were very extremely durable. Some folks in the original studies, from over 16 years ago, are STILL in remission and are cautiously being said to be “cured.” This new “FCR” combination rapidly became the gold standard for the treatment of CLL and it rapidly became the frontline therapy world-wide. And as it was, I too received the FCR in Denver in late 2002, despite its not being yet approved by the FDA for my disease. I was probably the very first person in that wonderful town to derive its benefits. By the way, rituximab was developed, in part, with the support of the Leukemia and Lymphoma Society.
In 2008, I was relapsing again, and by now was being seen by Doctor Keating himself, in Houston. It came time to treat me again, but when you’ve relapsed from CLL a time or two, there are no “best” treatments available. Just lots of confusing choices to decide among. But Dr. Keating told me there were a couple of studies available. I signed up for one, which was to involve harvesting my CLL cells, treating them to make them appear “foreign” to my body, and then reinfusing them so my own immune system would start killing off leukemia cells; in essence, immunizing me against my own disease. That was the theory. I was all set to begin this study when it apparently went awry somehow. I don’t know details at all, but suddenly that study was off the table. It rather sounded like there was an “adverse event,” as they say in med-speak, with another patient who had enrolled earlier than I had. But, that’s what happens sometimes in these trials. You don’t know before you start exactly how they’re going to turn out.
So, I instead signed up for another study which was open at the time, one which combined the previously mentioned “FCR” with an antibody called bevacizumab (Avastin). I took the combination for six consecutive months and at the end, was in a complete remission, one so complete I was said to be “PCR” negative, which meant that they could find no evidence of disease even at the molecular level. I wondered if I might be cured…but I knew better. This stuff just about always comes back.
But I was feeling well and wanted to start giving back to the researchers who were working behind the scenes on behalf of me and so many other folks like me. I had joined the Leukemia and Lymphoma Society and its fund raising arm, Team In Training (TNT) in early 2007 and had attended meetings, given short talks called “Mission Moments,” and spoken to people training for fund raising events, like marathons, half-marathons, triathlons, 100 mile bike rides and much more. I fully appreciated what they were giving up with the time they spent training, coming out early in the morning when they could have been sleeping in, and raising money for the Leukemia and Lymphoma Society. And they were doing it for me! And most of them didn’t even know me.
So in late 2008, to help pay back what they were doing for me, I joined them on the trails, early in the mornings. I started walking, first a mile or two, then three or four, then eight miles and eventually, I was walking (not running!) 13 miles at a time. I was doing half-marathons. And while I was doing all this training, I was asking for donations to the Leukemia and Lymphoma Society from friends, family, neighbors and colleagues. I found myself doing three or four half-marathons a year, and I raised several tens of thousands of dollars for the LLS.
I kept up this pace until mid-2011, when I started slowing down and not feeling well. I did my last half-marathon in San Diego that May and shortly thereafter was found to have greatly enlarged lymph nodes in my chest and abdomen. The disease had come back after three years of remission. And, what was worse was that it had come back as the 17p deletion variety, the absolutely worst subtype of CLL. My longevity at that point, if untreated, was said to be about 12-18 months.
Dr. Keating tried a new drug on me, one that had recently been approved for CLL, one called Arzerra, but we knew going in that it only had about a 50% chance of working in my situation. And, I fell on the outside of the 50% margin. It didn’t help me at all.
But, at that point Dr. Keating invited me to join a clinical trial of yet another new drug, one which had just come out of Phase 1 trials. This drug was so new it didn’t yet have a name. It went simply by its developmental code name, PCI 32765. By now I had swollen lymph nodes in my belly and chest which were up to eight inches in diameter. I looked like I might be pregnant! I had been hearing great things about this new drug and was happy to sign up for this trial. I started taking the PCI 32765 (which became ibrutinib and then Imbruvica) in March 2012 and it started working immediately. I could feel the difference in the pressure in my belly within the first week! It was amazing, truly amazing, to me. Imbruvica, as it’s called now, was also developed, in part, with support from the Leukemia and Lymphoma Society.
After about six months on this miraculous drug, I was feeling much better, except that one major side effect of it was joint pain. I tried to come back to my LLS/TNT teammates but found that each time I tried to train for an event, my joints, and especially my knees, hurt too much. So I had to give up that part of my association with TNT.
But, during the time I was actively doing TNT events and “running” my half marathons, a couple of our kids joined me and walked with me. They also raised money for the organization. And they have continued that practice even after I had to drop out.
Earlier this year when our daughter, Jen, heard that I had relapsed yet again and was going to have to get into yet another trial (as there are still no “best” or any single correct option for treating this disease after you’ve relapsed several times) she told us she was going to sign up for another event and, again, raise money for the Leukemia and Lymphoma Society. And to that end, she’s now been training and fund raising for several months, in preparation for her half marathon to be held in November. She gets up every Saturday at between five and six in the morning to go out and train. It gets very hot in Texas so she runs with her teammates early in the morning before the sun comes up. She and her teammates get nothing out of this except for a T-shirt and the personal satisfaction of knowing they are part of a greater mission. And that they are helping others, like me and so many other leukemia and lymphoma victims, who are waiting for new and better drugs to be developed. We are in never ending hope that a cure will be found to take these diseases away from us and our friends and families.
Meanwhile, for similar reasons our elder son, Jon, is in training for a leg of the Dallas Marathon relay, which will be held in December. He’s starting to train out in El Paso but will come to Dallas for the event and he, also, is raising money on behalf of the Leukemia and Lymphoma Society. He has the same issues with training in the heart and early in the morning. Hey, it’s hot in El Paso. But he’s dedicated. Additionally, he has the burden of training by himself and not with his team, which is 600 miles to the east in Dallas.
I haven’t asked my friends and family for any donations for several years now, but I’d ask that if you can, please donate something to the Leukemia and Lymphoma Society through our kids’ web pages, below. Hey, and if you look at Jen’s page (JMassaviol, below), you’ll also get to see a “cute” picture of me and one of our daughter as well. I will personally appreciate anything you can do for them and the many patients who will eventually benefit from the results of cancer research.
Yesterday I received the results of my recent bone marrow biopsy, and the smear is almost normal. That’s hard to believe after only a little more than three months on venetoclax, but it is known for clearing disease out of the marrow. It’s a great drug. But still…I’m probably looking at a stem cell transplant in the near future. I got a call from the transplant team at M. D. Anderson last week, and they’re already looking for a donor for me. I guess Doc Thompson has been in touch with them. I’m supposed to see them in a few weeks so we can talk things over. We’ll see what they have to offer. I’ll get another update out real soon to explain why a transplant may be in my best interests right now, despite the excellent results I’m having with the venetoclax.
Next (really, this time)—an update on our last visit to M. D. Anderson and the logic of pursuing a stem cell transplant despite my doing great on venetoclax.
“They always say that time changes things, but you actually have to change them for yourself.”—Andy Warhol [So, please help change things by donating to the Leukemia and Lymphoma Society through our son or daughter, or any other person you know of who is working for the goal of curing these diseases!]
Friday, August 19, 2016
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.
JUMPING THROUGH HOOPS
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 well 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, after all the delays I'd experienced (see my previous blog entry) 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 ibrutinib and I also knew that I apparently only had a 60% chance of responding to the venetoclax in the best of circumstances. In other words, I had perhaps 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 onto 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!
RAMPING UP THE VENETOCLAX
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 white blood 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 heart 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 venetoclax 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” for 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. But, 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, at about 2,600. My red cell count has come back from being a low 28% (normal for a male is more like 45%) up 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 are few to no side effects. No nausea (which is the most common side effect), 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 again 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 getting into. 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