I have been on the Ruxolitinib trial for two years now. It has been good so far.
The trial was designed to address the symptoms of CLL and prove, disprove, or measure its efficacy in individual patients. The requirements of the trial were that each person enrolled must not be treatment naive, meaning that they had to have received treatment under at least one of the chemotherapy, immunotherapy, or combination chemo/immuno protocols being currently utilized and manifest symptoms that interfere with the quality of life. With CLL, those symptoms include but are not limited to fatigue, bone pain, joint pain, night sweats, and the development and accumulation of auto-immune diseases which the patient had not known previously. There are others, too.
I had all of the above, the worst of which was a life-altering fatigue. Not all of my fatigue was caused by the CLL as I have physiological issues with sleep that compounded the fatigue. While a single fatigue issue may have been bearable, as we all suffer bouts of fatigue, the combination was awful. Having previously been treated with a combination chemotherapy/immunotherapy regimen of fludarabine, cyclophosphamide, and rituximab (FCR) which was the gold standard for treatment at the time, and having no other issues which might exclude me, I was a good candidate for the trial. I think it was a wise move for me.
FCR gave me a complete remission that lasted for 5 years, which means that for that 5 year period, by the most sophisticated laboratory measurements that Big-as-Texas Cancer Center (BATCC) could make, their hematological pathologists could find no evidence of the disease in my body. This was a good thing. Some people never achieve a remission, some had their remission last only a few months, some, like me had theirs last several years, and some fortunates who were treated the same time I was are still in complete remission. A lot of what determines their response to treatment and their post-treatment status depends on their personal genetics which plays a huge role in any cancer and its treatment.
Three years ago, my remission failed. A peripheral blood sample put through a lab test known as Flow Cytometry revealed that .09% of my bone marrow was involved in throwing off cancerous lymphocytes, or blasts, the white “B” blood cells that do not do their job, compromising my immune system and eventually…eventually…crowding out all the other blood cells if left unchecked.
We need every type of blood cell we have, and all in the proper balance. When one’s cancerous white blood cells start crowding out one’s red blood cells, the game is over. Usually, prior to that, the compromise of one’s immune system causes death by some secondary infection, not the cancer itself, though the cancer is the reason the secondary infection occurred and then proved to be fatal. I have been through all this before, and if you are a CLL patient, you are already aware of this…or you should be.
Perhaps it’s not judicious of me to say, “…you should be.” Many people with CLL just simply do what the doctors say, take their treatments when they are told they need to be treated, take the treatment type their hematologist/oncologist recommends with no questions, and then get on with the business of living, never giving it a second thought, or if so, never saying anything about it. Others labor under constant fear, perhaps unable to get on with their life, which is also understandable. Others, like me, must learn everything we can learn about the disease, its mechanisms, its treatment, the treatment outcomes, our life expectancy because of the disease, blah, blah, blah. A lot of what we understand as laymen is incorrect, but then, again, some of what the professionals currently understand later proves to be incorrect, too. We live in a world of flux and change. We don’t know everything. We are even capable of misinterpreting events so that our hindsight is not a hundred percent right, which is pretty wrong. We must learn to successfully navigate a world of decay, chaos, and random occurrences, and face these things with whatever fortitude we can muster, from within or without, as the world is not likely to change; it is we who must change.
One year after the flow cytometry revealed that my remission had failed, a second one indicated that 1.9% of my bone marrow had become involved. This is a substantial increase: an order of magnitude and then doubled in just a year. I couldn’t stand that same rate of increase very long. I was ready to do SOMETHING even if Dr. Gooday seemed to have a less-immediate concern than mine, which is the way with CLL.
The first standard of treatment of those with CLL who are not stage IV is “Watch and Wait.” This drives any cancer patient to distraction.
“I don’t want to watch and wait,” we all said. “I want this cancer gone. You treat me now.”
“Not so fast,” said all our hematologists as we sat on our hands to keep them from springing forward to throttle them in our frustration.
I suppose the first thing I had to learn is that my physician is not my enemy, which is a common mistake for one to make because he is the one bearing all the bad news. The prophets of old were not well received when bringing the Word of The Lord to a rebellious and recalcitrant people, either. The truth is the truth, even when unpleasant to hear. But it is the truth we must have if we are to make any sound decisions, and with CLL that truth is sometimes to watch the disease as it progresses and wait on any treatment until the symptoms become intolerable, or when our blood begins to get dangerously out whack as the cancerous cells begin to multiply exponentially. This is hard for us all, particularly those with type A personalities who are accustomed to making something happen. Not having a B type personality, I cannot judge how those with it may feel, but most folks won’t admit to having a B type personality and of those who do I expect they’d like to do something now as well. I don’t reckon anyone likes the idea of doing nothing when a cancer is attacking his body. With CLL, though, if you are in watch and wait stage, you are actually in a good place, as that means treatment is not required at this time. There are worse places to be.
Treatment has risks. There is the risk of it not working. There is the risk of it killing you. There is the risk of debilitating side effects. Somewhere amidst those extremes is where we most likely find ourselves, though the extremes are out there waiting to catch a few folks. Our hope is that the treatment will be completely effective and the side effects will be minimal. That was true in my case, though I had some extreme nausea, which is now just a bad memory. Ooops, I forgot about the shingles. I also had an outbreak of the shingles. No one wants that. Ooops, I forgot about the awful way those huge doses of steroids made me feel, which aren’t really side effects but just the way steroids work which doesn’t mean one feels any better for knowing that. Ooops, I forgot about my neutrophil (another type of white blood cell) count dropping almost to zero, which can be fatal in and of itself, and having to sequester myself so that I did not come into contact with any other human being for about a two week period. My wife brought meals down to my studio. I let no one in or out. If I went out, I had to wear a mask. I could have taken a drug called Neulasta which would have boosted my neutrophil production but it cost about $6,000 a pop and my insurance would not pay for it, to which this must be added: as long as you are worried about your checkbook you are not in as dire of straits as you could be. I chose to isolate myself rather than spend the money. Neither isolation nor Neulasta guaranteed any particular outcome. There are no guarantees; there are only probabilities and risks to be managed.
Every course of treatment or treatment type has the chance to close the door on that treatment option in the future, so avoiding treatment as long as possible is wise. Because I am on the ruxolitinib trial, I am taking the risk that I may not be a candidate for certain current, or new and improved treatments in the future. There is that risk. There are always risks. Being alive is fraught with risks; in fact, being alive is an adventure in peril, as peril eventually overtakes us and usually manages to do so seldom at the time or manner we had in mind. Welcome to the world, CLL patient. Welcome to the world, human beings everywhere.
We are currently working on a nearly identical job in nearly the same place for the same client as we were when I started the Ruxolitinib trial two years ago. I can tell the difference, though others have also noted the difference and have said so, putting it in a different perspective, jogging my memory of just how difficult my previous fatigue was.
“Dad, you’re not the same person you were two years ago,” said my son, Canaan, who works with me every day.
“What do you mean?” I asked.
“Two years ago, you’d be so wrung out at the end of the day you couldn’t even drive the ten miles to the hotel. I had to drive us. Now, we’re all just tired at the end of the day. You drive yourself. It’s remarkable, the difference.”
I hadn’t thought of it like that, but he was exactly right. It’s true…I’m tired at the end of the day. Sometimes, I’m tired at the beginning of the day only to be whipped when the day is over, but so are many of you. Most of the tiredness I have can be associated with anyone who is 60 years old, or anyone who works for a living, or anyone who has the strains and stresses of a job they have to deal with. I can remember being tired at the end of the day when I was a lot younger and didn’t have CLL. You? You ever get tired at the day’s end? You? You ever been tired as you start Monday morning on what you know is going to be a long and arduous work week? I thought so. None of us are immune.
Fatigue and a bone wearying fatigue caused by one’s cancer are different, though. In the world of electrical substations, there are protective relays that look at the electrical frequency, which in North America is 60 hertz (HZ), or sixty cycles a second for our everyday AC current. Most everything electrical we have is designed to work on 60 HZ. There are some motor drives which vary the motor speeds by varying the frequency, thus they are called variable frequency drives, and power companies mostly don’t like them though they have grown accustomed to them because of their permanent ubiquity. If some of the off-frequency power gets back on the power lines those protective relays in the substations can see it, which require programming of them to allow for some variance in HZ, particularly near large industrial installations where those types of motor drives are common.
If the frequency of the electricity rises or drops above a certain threshold deemed appropriate by the electrical system’s engineers, they react and take the substation off line, shutting the power off to lots of folks. Mostly, they trip out on under-frequency because of heavy electrical loads in times when electrical generation just cannot keep up with electrical demand. The whole electrical grid is a marvel of balance, engineering, and timing. Everything must be just so or your power will go out. I am proud to be a part of this industry and to be able to understand and appreciate the constant Herculean efforts required to ensure that when you flip the switch your lamp comes on. It seems so simple, but how things seem and how things are are not necessarily the same. It is sort of like deciding when to treat CLL or not, or how to treat it once treatment is required, or how to manage the risks of treating and not treating. Nothing is as simple as it seems, though flipping a switch is easy enough, and accepting the expectation that the light will come on when the switch is flipped takes no imagination at all. It is, after all, what we expected.
Having said all that, I used to have my personal power trip out just like a circuit breaker trips out on an under-frequency relay target. My personal operating frequency would drop and I’d just go OUT. There was no warning, just a target and signal to open the breaker, and in an instant I had no energy…the lamp went dark. It was never what I expected, but it is what I got.
I don’t get that much anymore, though there are occasions. When that happens, I just leave work early.
“Tripped out on under-frequency?” my brother will ask over the phone.
I just nod my head, too weary to speak, hoping he can see my nod through the phone. We all have limitations. Is it good to learn what they are and train to exceed them, if we can, or learn to live with them if we can’t.
So, my trip to Houston last week was good. My white blood cell count (WBC) had been creeping up over the last two years. I kept waiting, and keep waiting, for the exponential curve to manifest itself, but it hasn’t and it may not. Over the last four months my WBC has actually dropped. This is delightful news, though I am wary enough to know that it may not stay that way. Still, we learn to take good news where we find it.
“Some fortunate few of you who have been on this trial have had very positive outcomes,” said Gooday. “In some of you, it may be having a positive effect on the root of the disease, not just alleviating the symptoms. You are one of those fortunate few. Would you consider staying on the trial for another two years if it continues to be effective?”
Having no detectable side effects any longer, and having noticeable and remarkable improvements in the manifested symptoms, and showing possibilities of this being beneficial at the root of the disease, it did not take me long to give an answer.
“Yes,” I immediately said.
“Dr. Gooday, though my remission has failed, staying in minimal residual disease status (MRD) makes me happy,” I said.
He shook his head. “MRD status is not what I’m looking for. I’m looking for the elimination of the disease completely. I liked it when we could detect no trace of the disease in your body. That is the target I am aiming at and will not rest until we get a cure for CLL.”
If one cannot be disease free, then MRD status is the next best thing. I like Gooday’s goal, though. So should we all.
Like white-blood-cells-gone-bad, increasing exponentially, the number of new treatment therapies on the horizon are increasing at the same rate. CARs-T (which manipulates your own cell genetics and programs your immune system to fight CLL), a variety of immunotherapy drugs each targeting a variety of specific proteins that exist only on the cancer cells, and vaccine-like drugs which are a whole new world of possibilities are currently being studied here and abroad, with hematologists working like madmen trying to find the one thing that will work across the board, simply, effectively, and as risk-free as they can make it.
They are so close that none of them are willing to rest as they can see their goal right before their eyes. This is true of treatments for all types of cancers. Every advance in one area of immunotherapy for one type of cancer leads to an advance in treatment for another type of cancer, as cancer cells of varying types share many of the same bad proteins on their surface, most of them inflammation causing proteins, and inflammation is the cause of so many of our maladies.
Nearly all of us CLL patients who have been recently diagnosed or undergone treatment have had what is known as a FISH panel done. That stands for Flourescent In-Situ Hybridization. It detects specific genetic anomalies occurring in your CLL cells. Some indicate a worse prognosis than others. If you decide to start studying this on your own, be sure to look at the dates of publication of the articles. Anything older than about three years is nearly obsolete as far as life-expectancy is concerned.
There are five most common types of FISH panel determinations: 17p deletions, which means a part of chromosome 17 is missing: 13q deletion, which means part of chromosome 13 is missing: 11q deletion, which means that part of chromosome 11 is missing: Trisomy 12, which means that there is an extra leg on chromosome 12: and a normal FISH result. Of these, 17p is the most undesirable, followed a long way behind by 11q. A 13q deletion is good if one is to have CLL, because 13q patients have a indolent form of the disease which usually progresses slowly and typically responds well to treatment. Trisomy 12 and FISH normal have about the same response rate and outcomes, and are less desirable than 13q but more desirable than 17p or 11q. One thing about FISH panel results is that they are not set in stone and can change over the course of the disease. I mentioned this to Gooday, asking him if I were to need re-treatment, would we get another FISH panel done first, acknowledging that I knew that FISH results could change.
“Yes, we would,” he said, “But people with normal FISH panel results almost never change.”
“I didn’t know that,” I said.
“I may be the only one who does,” he said.
I liked that answer. I am in good hands and have been ever since I was diagnosed by Hemosapien in Meridian, whom I still see as he is a major part of my team. I never want to leave him or his clinic out as I talk about Gooday and BATCC… they have different missions and different tools available to them. Hemosapien treats all kinds of cancer patients and patients with other blood disorders. Gooday and the several other research physicians at BATCC have the luxury of devoting and focusing their entire careers on the treatment of and research for advancing the treatment of CLL. They need each other. Hemosapien needs all the tools Gooday and his fellow researchers can give him. Gooday and his colleagues at BATCC cannot treat all the people in the world with CLL. It is a symbiotic relationship. The more we all know, the better off we all will be. I salute them all.
And Dr. Gooday, it is no longer true that you might be the only one who knows that. You told me, and Debbie was right there with me, so for certain, that is now three of us. I expect there are several more.
There are other things beside FISH panel indications that are not good. Elevated CD38 (a protein), elevated ZAP-70 (another protein), and an unmutated IgVh gene all promise unfavorable outcomes, and they are permanent, not changing over the course of the disease. I carry all three, but the first two are really indicators of the third. I will carry an unmutated IgVh gene to my grave. If you clicked on the link I shared above, go back and see this if you are of a mind. It is specifically mentioned there. So, I don’t have a 17p deletion and that is good. But I have an unmutated IgVH gene and that is bad. Every thing cancer takes from you that medicine gives you back is mitigated by another thing cancer takes from you.
In the end, the result is the same whether we have cancer or not. To quote the old phrase referring to the dates on tombstones, “It is the dash between the dates that represents the life lived.” Do I worry about it? Sure. But, before I worry more, let me fix myself another cup of coffee. I will worry over just how I fix my coffee, too, especially now that The State of California, under its Proposition 65, is in a lawsuit trying to force Starbucks and other coffee vendors to post the following language on its coffee cups: “This product can expose you to chemicals, including lead, which are known to the State of California to cause cancer and birth defects or other reproductive harm.” This will help California lawyers make a lot of money and not help a single person avoid cancer or other reproductive harm.
There’s lots to worry about, but worry over things one cannot control is useless: perhaps uncontrollable, but still useless. Still, I will worry today as much about CLL as I will worry about coffee giving me cancer, California’s generous warning notwithstanding.
Nearly 10 years ago, I was told that the most I could expect was 7 years before succumbing to CLL. I am 3 years past my expiration date. In fact, there is no longer any expiration date that can be accurately determined until the date one actually expires. Sure, there are numbers and statistics, but you don’t know where you fit in those. Everything written about outcomes and time frames for potential outcomes is in a state of flux and they are all moving in the right direction. One should not spend their time in a paralyzing fear of what may occur tomorrow, because tomorrow may hold something of much more immediate concern than CLL. We all have concerns, but our concerns cannot paralyze us to living our lives, else CLL has claimed us already.
There is so much around us to be thankful for. Stop and make a list of them. Learning to be thankful for what one has can go a long way to helping reduce the impact of what one has lost. What is lost is gone forever. What we have can be lost, too, if it is ignored, or if we become so blinded by the fear of tomorrow that we lose sight of the wonders today holds.
Sound cheesy? Maybe so. If it is, then enjoy your cheese.
Me? I like cheese.
Some cheeses, though, I like better than others.
And Bleu Cheese? Like the oysters on the half shell I love so much, it is forever off my menu.
Velveeta is just fine for a country boy, where is falls slightly behind room temperature Red Rind Hoop Cheese, which gets me to the relevance of the photo at the beginning of the blog, since you may have been wondering.
My life-long friend, John, who now lives in Tuscaloosa, was born and raised in Meridian of a fine family and has always enjoyed doing things “elite” people find outrageous. On internet forums nowadays, John might be identified as what we call troll. He does things just to see people’s reactions.
A long time ago, at a wine and cheese tasting fund raising event for the Meridian Symphony, everyone was supposed to bring some wine and cheese to contribute. There were all sorts of fine wines and exotic cheeses. Partially obscured and left unmolested at the last table was the Boone’s Farm and Velveeta John had brought. To this day, I still think that is funny. John does, too. We have laughed about it for forty years. There are perhaps some who were in attendance then that thought, and still think, that John didn’t know any better.
That is the funniest part of all.
©2018 Mississippi Chris Sharp
PS – Ruxolitinib is currently on the market as Jakafi®. Produced by Novartis, the drug is a cytokine inhibitor targeting the enzymes JAK-1 and JAK-2. It is approved by the FDA for treatment of advanced cases of Myelofibrosis and for Polycythemia Vera. Though the drug is provided for me free of charge, the typical pharmacy retail price for those who use it is $14,000+. There is no generic version.