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.