Book 5, Chapter 2, Verse 10
November 7, 2014
I’ve been taking that near-miraculous drug, ibrutinib, for about 30 months now. I believe it has, quite literally, saved my life.
Just a little over three years ago I got very bad news. The CLL I had been fighting for nine years had mutated from a moderately aggressive form to the most aggressive form of the disease. I found that I had the dreaded 17p deletion, wherein my chromosomes had lost a gene called the “tumor suppressor” gene. Without it, the disease is very aggressive and especially resistant to chemotherapy. Most studies predict that without treatment, the expected longevity with this mutation is between 12 and 15 months or so.
The only treatment really known to work in this circumstance is a stem cell transplant (or bone marrow transplant; they are the same thing), which I knew would be a possibility at some point in my life, when nothing else was working for my disease, but I wanted to postpone a transplant for as long as possible since a transplant is not without risk. There is a fair chance of dying from the procedure, and this risk is generally quoted as being about 25% or so, depending on whom you talk to and where the procedure is done.
My doc at M. D. Anderson in Houston tried to treat my disease with a newly approved medication called Arzerra (ofatumumab) for a few months to see if it might work. But after four monthly treatments, it was clear that it wasn’t working. A CT scan showed that I had multiple tumors in my belly, chest, neck and underarms, the largest ones being about the size of oranges. It looked like it was time to see about that transplant, and so I did. I went to the transplant clinic at M. D. Anderson and was examined, filled out all the questionnaires, gave multiple tubes of blood and signed forms agreeing that I knew the cost could be upwards of a million dollars, which I would be responsible for if insurance didn’t cover it. Yikes!
But, the very next day I got wonderful news. I had been accepted into a Phase 1/2a study of a new drug, a drug so new it didn’t yet have a name. It went simply by the name PCI 32765. It had been tested recently on about 90 seriously ill folks with CLL and seemed to show great promise. I jumped at the chance to get into the study.
I began taking this drug, the first of its kind, and an orally active medication for CLL, in April 2012. My previous treatments for my disease, over the previous years, had all been IV chemotherapy, needing four to six months of therapy, several times every four weeks. But this PCI 32765 stuff…it was so easy. Three capsules in the morning and I was done each day.
When I started my treatments with the PCI 32765, it was in combination with Rituximab for the first six months. By the time I was able to start taking my first doses, the tumors in my belly had grown to be about 16 centimeters in diameter, about grapefruit sized. I looked pregnant. My belly was distended with tumor, I had large lumps in my armpits and had multiple tumors on the sides of my neck. I was very sick. But, within the first week of starting on the Rituximab and PCI 32765 combination, even before I was examined again at the clinic, I knew it was working. Within days I could tell that my belly was less distended. The tumors were shrinking that fast!
Indeed, when I had a follow-up CT scan three months after starting the ibrutinib (as the generic name of PCI 32765 came to be called) the tumors had shrunk by almost 90% of their volume. Within a year, the tumors were gone. During that time my white counts came down to normal, my red cell counts improved and my platelets stayed steady, though lower than normal, as they had been since my third round of chemotherapy in 2008.
The side effects of this near-miraculous new drug were, at least in my case, almost trivial. I had frequent pains along my joints, primarily in the small joints of the feet, hands, wrists and ankles. This was often accompanied by some redness, and the pain could be significant but almost always resolved within three or four days. Rarely did I take any medications for the pain. I also had some very minor skin rashes, a few small sores in my mouth on occasion, but not too much more. I have the fatigue that most folks with CLL seem to have, and I have all too frequent sinus infections, which are also very common, but that’s about it. Now, I know that other folks have had very serious, full-body rashes and more severe pains, some have had significant diarrhea, and some have had sloughing of their mucous membranes in the mouth and other places. But, I have been exceedingly fortunate in having so few symptoms. And, I think my experience is probably more typical than that of those folks who have had worse problems with side effects. In any case, the side effects are significantly less than could be expected of a bone marrow transplant. This is one amazing drug.
But, it’s not perfect. As I’ve mentioned, there is a small failure rate for some of us on this drug, mostly among the people like me with the bad mutation, the 17p deletion. But, I’ve been told it’s only about a 5% failure rate, with a few other failures occurring in the 11q deletion patients and a few others as well. Apparently some folks have developed a more serious form of our disease, with Richter’s transformation, where our disease transforms into the much worse “diffuse large B cell lymphoma” (DLBCL). So, ibrutinib is not a perfect drug, but nothing is when you’re treating cancers of any kind. But, man, is it good. I’ve been in contact with many folks all over the world and all of them who have started taking ibrutinib, except one unfortunate guy who developed DLBCL, are doing just great.
Initially, when starting the Rituximab and PCI 32765 treatments, we were going to Houston weekly. After five consecutive weeks, the frequency was reduced to monthly for the next five months. As my exams and labs began to normalize, the appointments went to every three months, then every four months…and at my last visit in August, after my two and a half years on ibrutinib, they told me to go away and not to bother them again for SIX months, sending me off with a supply of ibrutinib worth more than the car I was driving! I continue to take three capsules daily and the list price per capsule, now that it has been approved by the FDA, is about $92 each. So, six months’ worth of capsules is indeed worth a fair amount.
Kathy and I have been taking advantage of my/our good fortune and, after this excellent news, went on a 16 day river cruise in Europe, passing through Germany, Holland, Austria, Slovakia and Hungary. This was a very, very nice cruise and, despite having lived in Germany for seven yeas while I was in the Army, we saw many cities and places we hadn’t visited earlier in our lives. And, life for us has returned pretty much to normal again. The only continuing problems I have are the intermittent joint pains and the enduring fatigue. But, those are very small prices to pay for having access to this incredible new drug.
The standard three capsule daily dose is something several folks have been looking at. When this drug went through Phase 1 and Phase 2a studies, the only doses studied were 840mg and 420 mgs daily (six or three capsules a day). It was quickly found the three capsules work as well as six, so the larger dose was dropped. But, to my knowledge, no one yet has studied any lower doses. Doc Keating has mentioned wanting to study the efficacy of lower doses, and to study leukemia cell receptor saturations at lower doses, but the drug was controlled by the company and human use studies are exceptionally difficult to get approved. As they should be.
But now that the drug has been FDA approved, is widely available and can be prescribed by any physician, I know that there are people who are trying lower doses. I have a correspondent who, on his own, lowered his dose from three capsules daily to two because he was having horrible full-body rashes. His rashes have improved and, in the short term, his blood counts seem to be continuing to improve. And I have heard of another patient who was refusing any chemotherapy of any kind, who was convinced to try just one ibrutinib daily, and also in the short term, I hear that she is improving. Time will tell what the optimal dose will be. I keep expecting to hear of a clinical trial with one, two and three capsules a day, to see if they are, or are not, equally effective.
Meanwhile, the FDA has approved yet another oral drug, idelalisib, for use in CLL. And there are more in the pipeline. The stuff called ABT 199 is showing great promise and should be coming along soon. It’s the drug that Doc Keating said I may be switched to if I relapse while on the ibrutinib.
But, even as these first generation drugs are being developed and approved, there is now a second generation drug like ibrutinib (another BTK [Bruton’s tyrosine kinase] inhibitor) in trials. This drug is called ACP 196 and it is in Phase 1 trials in multiple centers right now, including at M. D. Anderson.
In other recent notes about this wonderful drug, I have recently heard news that makes it much more convenient to take. Originally we were given strict instructions to take it on an empty stomach, at least thirty minute before we ate, or two hours afterwards. But recently one of the researchers has said that the absorption is the same with or without food in your stomach. It just seems that there is less diarrhea when taken on an empty stomach. Since I’ve never had any issues with that at all, I now just take my capsules in the morning with breakfast. And, I’ve mentioned the CARs procedures in previous messages, where one’s T lymphocytes are modified to attack your leukemia cells. The folks at M. D. Anderson have been working on a specific type of CARs (or also called CART) called the ROR1 CARs. But, as of my last visit, it still hadn’t gotten into clinical trials, so I don’t think that possibility will be in my future any time soon. But, work on this is slowly progressing.
When I started this series of little stories, they went out solely to family and close friends, and though I had a fairly long mailing list, it was limited to about 150 folks. But, just a few years ago our kids convinced me to publish my messages in an on-line blog form, to make them easier for my friends and family to access. And this has had an interesting unintended effect! Other folks around the English speaking world, when Googling “ibrutinib” or “CLL” and other topics, have stumbled upon my stories and I have had contact with many other people with this disease, or the family members of folks with CLL. I have correspondents in England, Canada, Australia and across the USA. My stories have been read, on-line, by hundreds and hundreds of people. I know this because Google, who runs the blog site, keeps track of every click on my stories.
It has been a wonderful thing to share our stories with each other and to be able to commiserate when we had to. I have shared my experiences with lots of folks and have tried to judiciously dispense advice about what might be available and/or advisable for others with this disease. But, I’ve had to put a disclaimer at the top of my blog, noting that I’m really not an expert. I know, or at least I think I know, a lot about CLL as I’ve been dealing with it, reading about it and writing about it for almost 13 years now. But, I have to tell you, when I start talking with Dr. Keating about the details of CLL, or when I get into the research articles about CLL that are published in the hematology/oncology journals…I admit that I have trouble understanding a lot of it. And so, I can fully appreciate how non-medical folks would have difficulty comprehending so many of the details of this very complex disease. So I am very happy to try to help other folks understand what they are facing and what their options are. It is nice to be able to tell them now, after many years of having little real hope, that we live in a “golden era” for patients with CLL. There are now so many very effective and non-toxic options for us. Most of us shouldn’t have to have harsh chemotherapy and most of us should be able to avoid a stem cell transplant and its attendant risks. A cure is surely coming soon.
And, so, that’s all for this episode. I’ll be going back to Houston to be examined and have another bone marrow biopsy in January. My monthly labs tests done here at home have been completely stable and so I’m fully expecting that my check-up in January will be normal as well. If so, I’ll probably be continuing on the ibrutinib, as long as it keeps me disease-free. The manufacturer has agreed to keep its early test subjects supplied with the drug as long as we are willing to be examined periodically, as they need long-term data about its effectiveness and side effects. So far, we only have about four years’ worth of data on a few hundred patients. It’ll be nice when we have, maybe, ten years or more of data to show that it keeps on working for many, many years.
“Take therefore no thought for the morrow; for the morrow shall take thought for the things of itself. Sufficient unto the day is the evil thereof.” Matthew 6:34
“I have told you these things, so that in me you may have peace. In this world you will have trouble. But take heart! I have overcome the world. ” John 16:33