Friday, November 7, 2014

My Two and a Half Years on Ibrutinib

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Here’s hoping!


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

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

Tuesday, July 8, 2014

About that transplant...

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


“Work for a cause,
Not for applause.”

Tuesday, March 11, 2014

It's Your Choice

Dave’s Great Adventure

Book 5, Chapter 2, Verse 7

“It’s your choice,” said Dr. Khouri.

I’ve been riding the CLL roller coaster for twelve years now, and count myself as very fortunate to have been able to do so. Lots of folks with CLL don’t last this long. I’ve had some very low lows and some very high highs on this roller coaster, but among the highest times I’ve had was when I was accepted, almost at the last minute, into the ibrutinib with Rituxan trial at M. D. Anderson in Houston a couple of years ago.

I had just found out, a few months before, that I had developed the deadly CLL mutation called the 17p deletion, or the p53 deletion. They’re the same thing and they refer to the fact that my leukemia cells have mutated and have lost a part of my number 17 chromosome, the part which contains the gene (the p53 gene) which makes abnormal cells self-destruct when damaged. That gene is why chemotherapy works. The chemotherapy damages the cell’s DNA and so the p53 gene makes the cell die. Without that gene the abnormal cells continue to grow and are almost entirely resistant to chemotherapy, making the disease very hard to treat.

After we found that I had developed this mutation we tried some new chemotherapy but it didn’t work. I was developing very large tumors (enlarged lymph nodes, really) in my belly, under my arms, in my neck and in my chest. They were up to the size of a cantaloupe. With chemotherapy no longer working, I was just about out of options. All that was left for me in hopes of treating the disease was a stem cell/bone marrow transplant.

I’ve known since I got sick twelve years ago that a stem cell transplant would be my ultimate safety net when nothing else was working. But I’ve been extremely fortunate to have been able to ride the wave of new treatments and experimental studies from one relapse to the next and have never had to seriously consider a transplant. Now, a transplant can be curative and has cured many folks, but it’s something most folks only go to when they’re out of other options. That’s because the usually quoted death rate from a transplant, of the kind I would need, is about 25% or about one chance in four of dying from the complications of the transplant. Scary! And even if one survives the initial transplant, there is the very real possibility of long term problems with what’s called “graft versus host disease.” That’s the opposite of a person rejecting a transplanted organ. In the case of GVHD, the transplant is “rejecting” the person and it can cause anything from minor annoyances to major problems including death.

But, two years ago I was facing this decision. I had the deadly mutation, the 17p thing, and I had failed my last ditch chemotherapy. I was out of options. So, Kathy and I were in the Stem Cell Transplant Clinic at M. D. Anderson in Houston, signing me up for one. None of my siblings match me, so the best I could hope for would be an inelegantly named Matched Unrelated Donor transplant, or “MUD.” We signed all the paperwork and set the wheels in motion for a transplant in the coming weeks or months, once a suitable donor could hopefully be found.

But, the very next day I was accepted into the new ibrutinib study! And so we put the transplant on the back burner while we waited to see how I would do on this new drug, which was so new that at the time it had only been tested on about 90 other folks, worldwide, and didn’t even have a name. Back then it was called PCI 32765, its developmental code name. Since then it has acquired a generic name, ibrutinib, and more recently, a trade name, Imbruvica.

And I have done incredibly well on this new drug. I take three capsules daily (at a cost of $91 per capsule or $273 a day) and I could tell within days that it was working. I could feel the swollen nodes shrinking and my swollen belly getting smaller. When I started the drug 90% of the white cells in my blood were leukemia cells, and 60% or more of the cells in my bone marrow were leukemia cells. But, I had a bone marrow biopsy just a couple weeks ago and, incredibly, there is no evidence of leukemia remaining in my bone marrow! This is just amazing news.

But, as more people have started taking this near-miraculous drug, and as the early participants have been on it longer and longer, the researchers are finding that many (or perhaps most… I really don’t know for sure) of the patients with the 17p deletion (and some with a few with other chromosome types, too) seem to be failing the drug after about 30 to 36 months on it. I’ve now been on it for about 24 months.

That brings up a dilemma for me. I’m still doing just great on the drug and am taking it daily with minimal side effects. But, if the experience of the folks who have been on it longer than I have applies to me, we might expect that I, too, will fail the drug and have a progression of my disease within the next year. And if I do, what would be the next drug to try? Well…no one knows. There are lots of new experimental drugs out there which are being tested on various groups of patients with CLL, but there is no known therapy which is “best” for people who have failed the ibrutinib. Anything we might try would be a shot in the dark. There just isn’t any data that I know of, indicating what might work. That is, if anything at all will work.

Meanwhile, I’ve been going back to visit the stem cell transplant folks periodically, about every three to six months or so. The visits have pretty much been of the “Hi, how are you doing, see you back in three (or six) months!” variety. But it seems they’ve been following my progress more than I realized. They know that I have the p17 deletion, and when they learned that those of us with that particular chromosome type are beginning to show signs of failure on the ibrutinib, they knew, before I did, that I might need a transplant in the near future. So, they went out and completed the search for a donor for me. And now they have one lined up, apparently.

So, going back to the bone marrow biopsy I had recently, the one which didn’t show any leukemia at all. It seems that now that I’m in clinical remission, with “clean” bone marrow, I’m in just about optimal condition for a stem cell transplant! That’s quite a dilemma for me, as I feel and look normal right now and don’t feel like I’m so sick that I need to take a chance on a stem cell transplant. But, I’m told that if I wait to see if/when I relapse, I’m likely to develop a more aggressive form of the disease and it could be more difficult to have a successful transplant. Dr. Khouri, in the transplant clinic (one of the pioneers in the field, by the way) is strongly urging me to do the transplant now rather than waiting. But, as he said at our last visit, after explaining the risks of waiting, “I think we should do the transplant now, or we can wait and see what happens. It’s your choice.”

So, that’s my dilemma. Get the transplant now and take a chance on the known risks, or wait to see “if” I relapse and take a chance of having a lower chance of a successful transplant at a later date. I’ll wait at least a couple of months until I see Dr. Keating again in May, when I’ll present him with my laundry list of questions and decide, as best we can, what I should do right now. And, if I don’t go the transplant route now, what he thinks might be my next steps in treatment if/when I fail the ibrutinib.

Meanwhile, there’s more news about ibrutinib, which is now called Imbruvica. In mid-February it was approved by the FDA for use in patients with CLL, but the approval was for patients who have failed at least one prior mode of therapy. In other words, you have to go through chemotherapy at least once and fail it before you’ll be approved for the less toxic Imbruvica. That’s counter to what the CLL experts are wanting to do as I believe they would like for everyone to be able to avoid chemotherapy entirely. That’s because chemotherapy damages cells and suppresses immune systems. Hopefully, Imbruvica will eventually be available for anyone who needs it as their front line therapy.

And that’s the story for now. We’ll have to decide fairly soon whether I’ll be going for the transplant or whether we decide it would be safe and not unreasonable for me to wait a while longer to see how I do on continued Imbruvica therapy. And see if a logical and effective follow-on treatment shows up. More later…probably in May.


Friday, January 3, 2014

Ibrutinib Update

Dave’s Great Adventure

Book 5, Chapter 2, Verse 6

I’m still doing fine but a lot of news has recently come out about the new, experimental drug called ibrutinib, so much so that I thought an update on it and other related topics is needed. This will be more of a technical update than a personal one.

First, and foremost, the FDA has approved ibrutinib to be sold on the open market and not just to be used in clinical trials. But, quite surprisingly, to many folks at least, it was approved, not for chronic lymphocytic leukemia (CLL) as expected, but rather for a rare and aggressive disease called a mantle cell lymphoma, about which I know very little. Approval of the drug for the treatment of CLL is still expected in the coming months, but with its approval for mantle cell lymphoma (MCL), that is almost a moot point. With the drug on the market now, physicians are pretty much free to use it as they want by using it “off label.” That means they can use any approved drug for other diseases if they feel there is a benefit. There are many examples of off-label use in medicine, such as antidepressants used for peripheral neuropathy, narcotics used to slow down over-active bowel function and many, many other examples. I have already heard of one patient who will now be getting ibrutinib for her Waldenstroms macroglobulinemia, for which the drug is showing great promise. But, I don’t even know if the company has applied for permission to be used for this disease. No matter. It’s now on the market.

And, now that it’s more widely available, it has a trade name. When I first started taking this drug it was still going by its company’s in-house development code, being called PCI 32765. Then, a few months later it was given its current generic name, ibrutinib. But now it has an official trade name of “Imbruvica.” And with that name comes its current marketing price, $91 per capsule. Those of us with CLL take three capsules a day, which comes out to about $8200 a month, or close to $100,000 a year. I believe the folks with MCL actually take four capsules daily but I can’t be sure of that.

And much more specific information is now available about how it, and many other drugs and procedures, are working against so many blood cancers and lymphomas. The American Society of Hematology recently concluded its meeting in New Orleans and all of the abstracts of the hundreds of presentations are now available on-line, for your review. It includes many interesting findings and nuggets of information, with a great deal of information about new and novel treatments for CLL. If you’re interested in taking a look at all or some of the abstracts, look here:

There is a search function which will allow you to search out the topics of most interest to you. I have to warn you, these are specialized topics written in the lingo of the specialists and some of the data are hard for us amateurs to decipher.

But there are several abstracts (which are just summaries of the presentations, not the entire article) which are of great interest to me. First, Dr. Jan Burger, who is the lead investigator of the study I’m in presented the official findings thus far. You can see it here:

I learned a great many things. As I have stated several times in my updates, when in Houston I generally ask how the other 39 folks in the study are doing. I am routinely told that everyone is doing fine. But, I don’t know if I’m asking the question too generally, or if the answers I get are just too general, or if (probably) the folks I’m asking just can’t tell me about the other study participants. But, what I have learned is that all of the other patients in the study are NOT doing just fine. In fact, of the forty original patients in the study, four are now dead. They are reported to have died of unrelated infections; sepsis, pneumonia and cardiovascular failure. Further, four more dropped out of the study for other reasons; two for ibrutinib related complications like mucositis (inflammation of the mucous membranes in the mouth, bowels, etc.) and a subdural hematoma (remember that ibrutinib inhibits platelet function and the clotting process), another with disease progression and one left to have a stem cell transplant. I have to assume, but do not know, that the person who left to have the stem cell transplant must not have been responding well.

However, despite these problems in eight of forty patients in the study, we have to remember that the study recruited the sickest of the sick. All the patients in this study had very bad prognostic indicators. Most had the 17p deletion, the 11q deletion and/or had failed multiple other therapies. Despite the loss of some of our group, the study reported a 95% overall response rate (complete or partial remissions) with 80% of us remaining on the drug without disease progression after 14 months or so. This is still a remarkable response rate in folks who are very high risk and, essentially, have no other options except that of a stem cell transplant.

If you look at this paper, it mentions that most of the study subjects were IGVH un-mutated. If you’re looking at this message you likely know that having the IGVH mutation is considered a very good prognostic sign, so it’s not much of a surprise to see that most of these patients in the study, who are generally pretty sick, do not have the mutation. However, note that Dr. Burger says one patient does have the mutation. Hey…that’s me!

This brings up another peripheral study that was presented at ASH. A researcher studied the relationship of the “protective” effects of having the IGVH mutation against the very deleterious effects of having the p53 deletion/mutation (I have both). They found that if you have the p53 deletion, having the IGVH mutation doesn’t seem to confer any protection, the deadly effects of the p53 deletion being the dominant factor. Too bad for folks like me.

Another study of ibrutinib which bears reading and studying is one presented by Dr. Susan O’Brien, also from M. D. Anderson. You can see her paper here:

In Dr. O’Brien’s paper, they have apparently combined the results from the Phase 1 study of ibrutinib, which had 108 patients in it, with the forty of us in the Phase 2 study, to give a total of 148 patients. She breaks the data down according to whether the patients had previous treatments and had relapsed or were refractory to treatment (RR) or whether they were getting their first treatments, being “treatment na├»ve” (TN). She further breaks the data down into the patients’ ages, number of previous therapies, time on the drug and more.

They have found that the serious adverse events decline after the first year and that most patients tolerated the drug pretty well. After about two years on the drug, 25 of 31 TN patients were still taking it and only one had shown disease progression, with no deaths noted. On the other hand, of the relapsed patients (RR), only 68 of 117 (58%) were still on the drug and 21 had noted disease progression. Notably, there have been 11 deaths in this RR group of 117 patients. However, the drug shows great promise, as the overall response rate was about 88% for the whole group, with most patients showing a partial response or better. She noted that after more than two years (average 27 months) on the drug, of those patients who had achieved at least a partial response, the median duration of response (DOR--the average time it takes patients to fail on a drug) had not been reached and could not be calculated as 76% of the patients were still alive without disease progression. That’s an amazing statistic. And a very hopeful one. I suggest you take a look at her abstract if you’re on this drug or considering taking it.

One last abstract I’d like to mention is one relating to the upcoming therapy called the Chimeric Antigen Receptor (CAR) procedure which is very exciting and is being studied in many places. It may be able to be a cure for many malignancies and is being studied mostly for leukemias at this point. It enlists the patient’s own immune system to seek out and kill the diseased cells. I won’t describe it here, as I’ve mentioned it previously and much more about it can be found elsewhere on the internet.

This procedure was pioneered by Dr. Carl June’s folks at the University of Pennsylvania. His early study of three patients resulted in two of them apparently being cured of CLL, though they remain immune deficient. In any case, it is interesting to see what percentage of the study patients are responding to therapy. This abstract also comes from Dr. June’s group. You can see his ASH abstract here:

This shows that, although the procedure has some excellent results, it doesn’t always work. Of 24 CLL patients who underwent CARs therapy recently, only 5 had complete responses, 7 had partial responses and 12 had no response. The results were a bit better for pediatric patients with ALL. Of 14 patients, 8 had ongoing complete responses and four have relapsed. However, it needs to be remembered that all these patients were desperately ill and essentially had no other options. My point, though, is that for all the excitement surrounding CARs, this procedure is in its early stages and is not a cure for all who enter into these studies, with possible complications, deaths, relapses and such. But, it still holds great promise for the future.

I’m still doing quite well and will be going back to Houston for another check-up and bone marrow biopsy in about six more weeks. Meanwhile the blood counts I have been getting monthly here in Denton are remaining pretty much normal. Hopefully I can give you another good report next month.