Book 5, Chapter 2, Verse 4
It’s been way too long since I last wrote in this journal and long-running story. When I go long periods of time without writing, it has always meant that things are going quite well, as it seems to me that there’s nothing worth writing about. But folks who read this journal but don’t have any other contact with me often don’t know whether I’ve just stopped writing, have died or maybe have left the on-line community. For this I apologize. I should let folks know when things are going well just as often as I do when they aren’t going well. But for the last many months, everything has been going extremely well.
I am now in clinical remission. Note the “clinical” qualifier. Most folks with cancer look forward to the day they are in remission, as for most diseases, like breast cancer, bowel cancer, prostate cancer and so on, that word equates to an eradication of their disease. But I am in “clinical” remission, and happy to be so. With my particular disease, that does not mean my disease has been defeated and is gone.
When I go to M. D. Anderson for my checkups, my blood tests and my physical exams are normal. So, “clinically” I appear normal and in remission. However, if one does a flow cytometry test on my blood or bone marrow, closely examining the cells in my blood, we find that there are still substantial numbers of leukemia cells in my body.
In fact, the aggressive form of leukemia which I have is still growing just fine within my bone marrow and lymph nodes, but this new wonder drug, the PCI 32765 (ibrutinib) is, essentially, whacking the abnormal cells as fast as they form by keeping them from hiding out in the nodes and marrow. When they’re out in the bloodstream, unprotected by the “microenvironment” of the lymph nodes, they die on schedule, like they’re supposed to. So, they don’t have the opportunity to harm me. Because, the way the cells of CLL harm you is by accumulating in large numbers in the bone marrow and lymph nodes, forcing out the normal blood cells we depend on for life; our red cells, our bacteria fighting white cells and our clot producing platelets. Now, with this new drug, they don’t have that opportunity. My lymph nodes are shrinking and my marrow is clearing its accumulated CLL cells.
I was declared to be in “clinical remission” last November, after about eight months of taking the ibrutinib, and after completing a six month course of Rituxan, the antibody which also attacks leukemia cells. Since that time I have had periodic blood tests, physical exams, another chest and abdomen CT scan and bone marrow biopsy. All is looking good. No…actually, all is looking great!
All of my blood test numbers for red cells, white cells, platelets and neutrophils either have normalized or are normalizing. My platelets, which hadn’t been less than half of normal for years, are now a little over 100,000. Normal is about 150,000-250,000 or more. And my most recent CT scan shows continued shrinkage of my lymph nodes. You may remember that I had masses up to 16 (about 6-7 inches or so) centimeters in size in my belly and many others in my neck, underarms and so on. They are continuing to shrink, even after having been reduced to about 12% of their pre-treatment size after just the first three months on ibrutinib. No one can feel any masses any longer.
So, the clinical trial I signed up for was to last a period of one year. In the body of the multi-page “informed consent” which I signed there was a sentence saying that at the end of the study year, if I was doing well, I “may” be allowed to continue to take the drug. And, I have done so. Though I am now into my fifteenth month of ibrutinib, I am still receiving fresh supplies of it from the manufacturer, Pharmacyclics (in case you’d like a stock tip!) at no cost to me, M. D. Anderson or you taxpayers. I have asked how long they will continue to provide it to me, and other study patients, as I’m led to believe that the capsules, of which I take three a day, cost about $100 each. That’s about $100,000 a year.
But I’ve been reassured that as long as I continue to show up for exams on schedule and get my blood and bone marrow tested periodically, I’ll continue to receive the study medication at no cost. And that’s very important to me and the other folks taking this drug, because we have limited options at this point. If we go off the ibrutinib, the disease will be back very rapidly…because it really never left. Without the ibrutinib, I would only have a stem cell transplant to fall back on, with all its inherent deadly risks and side effects. But, having helped the researchers prove that this stuff works in the short term ( a year or so) I am now moving into a longer term study of the drug, helping to see if there are any serious side effects with longer term usage. And, just as importantly, finding out if the disease figures out this drug and develops a “work-around” to once again become aggressive. We also don’t yet know how long it’s safe to take the drug nor what, if any, more serious side effects may be lurking as the months and months add up for those of us lucky enough to be currently using this stuff.
But the side effects, at least in my case and in those of people I have corresponded with, who are also on the ibrutinib, are very tolerable. I still have occasional migratory joint pains and they continue to be primarily on my small joints, like fingers, hands and feet, but I have had a few days of significant pain in my left knee. But, thus far the large joint pain has been a one-time occurrence. I have had a couple of significant bloody nose incidents, but nothing I couldn’t handle with home therapy like pressure and rest, and one small bleed into the white of my left eye after rubbing it too hard or something. One drug side effect we know of is that ibrutinib inhibits our platelets’ function so you may tend to clot more slowly. This really hasn’t been a significant problem for me, however. I now tend to avoid the non-steroidal drugs like Motrin, Naproxen and such, to minimize any bleeding issues which those kinds of drugs can cause.
And as far as I can determine with all my questions, just about everyone that’s taking this stuff is doing well. That’s just incredible, that such a huge percentage of folks on this trial drug are doing extremely well. With most new drugs, if you see a 30% or 40% response rate, that’s considered pretty good. But to have an 80-90% response rate! Just amazing.
The drug is proving to be so effective that it is being “fast-tracked” by the FDA and may be available for widespread use by the end of this year. Already there are multiple “Phase 3” studies going on, comparing this new drug with older, more proven drugs. If it works better, or at least as well, without undue side effects, then it should be approved.
And there’s more good news for folks out there with other B-lymphocyte diseases. The ibrutinib is looking like it’s pretty effective in treating mantle cell lymphoma, Waldenstrom’s macroglobulinemia and a couple more diseases, too.
And if it turns out that ibrutinib can’t be taken indefinitely for my disease and others? Well, there’s more! In the last couple of years you may have heard of the new CARs process for treating leukemias and other diseases. First, however, a little explanation about what “CARs” really means…because it’s so much like science fiction.
“CARs” stands for “chimeric antigen receptors.” What researchers have been able to do is train a patient’s own white blood cells (the T lymphocytes, which are distinct from the B lymphocytes that make up CLL cells) to attack and kill cancerous cells. For ease of understanding it might be best to understand that the “T” lymphocytes originate in the Thymus gland, and kill tumor cells and viral diseases and the “B” lymphocytes originate in the Bone marrow and make antibodies. That’s not precisely correct but it may help you understand how they are different.
“T” lymphocytes normally try to rid the body of foreign materials, including tumors, like warts, for example. But cancers hide themselves well and look like normal tissue to the T cells so they aren’t attacked. What our wonderful researchers have done is to devise a way to make the T cells search out and kill any abnormal cells they find.
What they have done is reengineer the T cells by adding a modified HIV virus in a patient’s own T cells, which have been collected previously. This virus carries with it genetic information which has been added, making the T cells search for a specific protein receptor on the surface of the target cells; in this case, it would be the CLL cells. When the T cells have been modified, they are then put back into the patient from whom they came, and they go about their business, tracking down and killing CLL cells. This procedure was first performed by Dr. Carl June in Philadelphia a couple of years ago, and he made national headlines by apparently curing a couple of very ill CLL patients of their disease.
This is, however, very complicated and very, very expensive and labor intensive, as each treatment can only be used in one patient, the one who provided the T cells. So every patient has to have their own batch of modified T cells made.
This procedure has been used in a handful of patients so far, probably less than a couple dozen, I think, but there have been some dramatic results; some apparent cures of desperately ill patients and some significant improvements in others. But, there have also been patients who have relapsed and a few who have died, so it’s still not something everyone can, or necessarily wants to, sign up for right now. But, this technology is improving every year. The folks at M. D. Anderson are working on doing this procedure in the coming year or so and have an improved methodology in mind.
At the risk of going on too long about the CARs stuff, let me add one more thing, the difference between the early CARs procedures, as done by Dr. June and others, and then procedure that the researchers at M. D. Anderson have in mind.
The early CARs procedures trained the T cells to look for a surface receptor called CD19, which appears on all CLL cells. But the CD19 receptor, unfortunately, also appears on all normal B lymphocytes. So, the few folks who were treated with CD19 CARs cell have had their disease apparently eradicated, but those same wonderful treated T cells, which are hunting down and killing the leukemia cells are also hunting down all normal B lymphocytes, which make a person’s antibodies. So, their disease is gone, but now they can’t make antibodies. So, they are given IV infusions of what’s called “gamma globulin” on a regular basis. This is serum collected from the general population which is rich in antibodies.
Now, what the folks at M. D. Anderson are going to do is train the T cells to go after a different receptor, one with the enigmatic name of ROR1. This is important, as this receptor is only found on immature cells, like cancer cells and some other cells which are early in development. In theory, T cells modified to kill only cells with ROR1, like all CLL cells, should not also destroy normal B lymphocytes, our antibody producers. This will be a huge step forward in CARs therapy. This study is about to begin down in Houston, within the year, I believe.
I’m going to finish up by referring back to my last “adventure” message, in which I related how lucky I’ve been in getting where I am in my treatments for CLL. Many of you wrote back saying, essentially, that I had “made” my own luck, by my planning, researching and investigating options for treatment. And, indeed, in many ways I have been able to affect what treatments I have gotten and where I have gotten them. But I’m also lucky in whom I choose for friends, as I have friends and family all over the US and in Europe too, who are interested in what’s happening to me and many, many of these friends are praying for me on a regular basis. And they’ve added me onto prayer lists at their churches. This is important as I find it impossible to pray for my own health. Or to make deals with God, “If you’ll spare me, I’ll….” I find that seeming, somehow, to be selfish. I figure if I’m really worthy of prayers, others will intercede on my behalf. And, indeed, they have and look at the results!
So, I’m on autopilot for now, taking the ibrutinib at a dose of three capsules a day, adding up to what has rapidly become the standard dose of 420mg daily. I’ll be going back to Houston for another checkup in August to get some, hopefully, routine labs and an exam unless something changes between now and then. And if something does, I’ll be back with many more details than you’ll really care to read!
“You walk down the street and you feel intensely alive. You’re ‘Oh, look at that leaf!’ You’re looking around and you think, ‘I’m alive. Ain’t it amazing?’ ” --Wilko Johnson, former songwriter and guitarist for the ‘70s band, Dr. Feelgood, on how he feels since being diagnosed with terminal pancreatic cancer and having just months to live. He’s embarking on a, literally, a farewell tour. He says he has never felt more alive. “The 65-year-old musician says that in the weeks since his diagnosis, he’s been unexpectedly happy—‘In fact it amounted at times to euphoria. I suddenly found myself in a position where nothing matters anymore. I’m a miserable so-and-so normally…I’d be worrying about the taxman and all those things we worry about that get in the way of real things. And suddenly it doesn’t matter. All of that doesn’t matter.”