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