I’m going to see my hem/onc tomorrow for a routine visit, a three-months-after-Rituxan-treatment checkup. There is a certain ritualistic element to the physical examination -- the fingering of the underarm nodes, the tapping on the liver, the measuring of the spleen. The latter is, to me anyway, a mysterious process, not unlike the reading of entrails performed by an ancient priest. There is a certain degree of poking and prodding and tapping and cocking of the ear (to listen through a stethoscope) and it concludes with a solemn pronouncement, usually something like “5 centimeters.”
If someone had told me years ago that this sort of thing would be routine for me, like going to the grocery store, I wouldn’t have believed them. And yet it is. From greeting the receptionists, who I know by name; and the woman who draws the blood, with whom I have made Dracula jokes during Halloween; and the nurse, with whom Marilyn likes to discuss how cold and uncomfortable the office is kept, it is all easily familiar. And therefore not too scary, really. Even the bald-headed women exiting the infusion room and shuffling past the reception desk, stopping to dip their fingers in the candy bowl -- where one can, with sufficient fishing around, usually find Tootsie Rolls -- don’t bother me anymore. These are my people. Cancer, schmancer (as Fran Drescher says in her book of the same name.)
My doctor is the newest component of the experience. Readers may recall that she took over the practice of Dr. Chopin, my previous hem/onc who decided to leave medicine. My new doc -- we’ll call her Dr. Belle -- comes from the South, so she has a certain charm and a slight accent to go with it. I could not ask for a less pedantic, more open-minded physician, and so I am pleased on any number of levels. Visiting Dr. Chopin often required a certain amount of mental preparation and voluminous abstract-printing and organized note-bringing -- for she was forever wanting to treat me with the hard stuff (she had been trained at MD Anderson) and I was forever wanting to avoid it and forever having to make arguments for doing so. Dr. Belle presents no such challenge. She and I are on the same wavelength. She once said something to me about how unfortunate it is that oncologists have to treat people with poisons. She understands that, especially with CLL, there are no magic answers, and that treatment can sometimes do more harm than good.
Alternate universe me
I didn’t always have it so easy. My first hem/onc, Dr. Lippencot, made Dr. Chopin look like a libertine. Readers may recall that her answer to everything, including “What time is it?” and “How about them Diamondbacks?” was “fludarabine.”
Readers also know that I fired Dr. Lippencot and found Dr. Chopin and that I have had 25 infusions of Rituxan since January 2004. It has now been 40 months since my diagnosis at Stage 2 with a swollen spleen, extensive lymphadenopathy, and a lymphocyte count of about 130,000. And for 36 months I have been playing the treatment game, which in my case can be described as “softball with CLL.”
The instant replay: Rituxan has been my sole treatment; my lymph nodes have reached the 3-4 cm range, my spleen has gotten as large as 9 cm below the costal margin; my platelets have slowly declined from the middle to the bottom of the normal range; my hemoglobin has always been normal, and I have had no B symptoms. In 2005, I learned that I am IgVH unmutated; my March 2006 FISH test showed that I had developed the 11q deletion (24%) after having had a “normal” karyotype; and I have maintained a blessed CD 38 negativity which was last measured at 1%.
With those prognostic markers, or at least the first two, there are doctors at big, well-known places who have suggested I look into RF or RFC sooner rather than later. I have avoided this, of course. For as helpful as it might be to know what often happens in unmutated, 11q patients -- conventional wisdom says the disease progresses quickly; remissions are not so long-lived -- it is wrong to assume these results will be true in the same way and in the same time frame for all patients. Heterogeneous disease, heterogeneous results.
And so there are two lessons I have taken to heart from my study and experience with CLL: Treat the patient, not the numbers. Treat when the clinical symptoms demand it, not on the basis of prognostic tests alone.
Prognostics tell us a lot, but they do not tell us everything. Deletion 11q is much bemoaned in the literature, but I know a few patients who are doing quite well with it, and with softball treatments for it. Or, to put it another way: We understand more than we used to about CLL. We have gone from the Dark Ages to the Industrial Revolution. But we have yet to enter the Space Age.
There is no way to know for sure how my Rituxan use has affected the course of my disease. There is no control to my clinical trial of one, no alternate universe in which I did something else and saw the results. But I did get to thinking recently about things doctors wanted me to do that I avoided doing and how they might have affected me. Here’s a rundown of my alternate lives:
Life #1: In October 2003, a month after diagnosis, I followed Dr. Lippencot’s advice and used fludarabine as a single agent. I got an excellent response -- one’s first response to treatment is usually the best -- and entered a fairly deep remission that lasted until the start of 2005. (I had neutropenia and a cough that wouldn’t go away, but I managed to ride it out.) I was retreated with fludarabine and this time with Rituxan added, as Dr. Lippencot had finally gotten around to reading some studies from Ohio State that I had begged her to consider. This remission wasn’t quite as deep as the first, even with the Rituxan, since I was showing some disease resistance to fludarabine. But the remission has been holding up pretty well, and I am only now slowly coming out of it. I will probably need retreatment later this year and there is concern that I may be fludarabine refractory, and I realize that my choices for treatment have narrowed considerably. Oh, and my January 2007 FISH test brought most unpleasant news: deletion 17p, which occurs in 40 – 50% of patients by the time they are fludarabine refractory.
Life #2: In January 2004, I began RFC on Dr. Chopin’s advice. I got an excellent response -- might even have been minimum residual disease (MRD) negative or close had we tested for that. Being youngish and strongish, I sailed through treatment. The hard part came when squamous cell skin cancers struck like lightning and required surgery on my left temple, leaving an ugly scar; there is concern about these cancers recurring, or metastasizing internally, and I have been under the nearly constant care of a dermatologist. Were it not for this, I might have been able to forget I even had CLL, since the remission was so lengthy. But last fall my absolute lymphocyte count began to creep up just a bit. It’s only slightly above normal now, and the nodes in my neck are returning just a little. Treatment in 2007 is likely -- and a repeat of RFC appears to be out, since I can’t expect it to work too well the second time. There’s Campath, but my T cells are already in the pits from the fludarabine, and I can’t risk my skin cancer running amok again, which is what it does with T-cell suppression. Then again, Campath is just about my only option now, since my recent FISH test brought most unpleasant news: deletion 17p, which is pretty much resistant to everything but Campath and steroids.
Life #3: In October 2005, having done Rituxan alone with fewer results over time, I began R + CVP (cyclophosphamide, vincristine, and prednisone) on Dr. Chopin’s advice. It reduced the nodes considerably, but my fingers are still numb as I type this; I worry the peripheral neuropathy from the vincristine may be permanent. The remission, which did more for the nodes than the marrow, was incomplete and lasted about a year; now that that the nodes are coming back Dr. Chopin wants to start RFC. I felt fine before R + CVP and I worry about whether my quality of life will suffer from RFC as well.
Life #4: In May 2006, having done Rituxan alone with fewer results over time, I began RF on the advice of a CLL Research Consortium doctor. I got an OK remission, but having been previously treated with Rituxan, it wasn’t quite as deep as it might have been had I used it as a frontline treatment. I don’t know how long I’ll get out of it -- a 2005 Ohio State study indicates 22 months as the median progression-free survival for unmutated patients with “high risk” cytogenetics (11q and 17p) using RF as a first-time treatment, which I’m not. At any rate, the doctor assures me that after relapse I will be eligible for some interesting clinical trials. In the meantime, the nodes are down. I had a FISH test this month and, thankfully, it showed no 17p deletion, just the old 11q. Maybe I’m being paranoid, but sometimes of late I think I have a sort of lumpy feeling in my abdomen. Richter’s Transformation from CLL to large cell lymphoma only occurs in something like 3 – 5% of all patients -- and 12% of patients who have been treated with fludarabine. It can’t happen to me, can it?
The lessons learned
Clearly and simply: Not one of the above treatments would have been to my advantage, so far as I can tell. Here I am with Rituxan, a bit chunky in the neck, but with an excellent quality of life and no burned bridges (though the old wooden Rituxan rope bridge is missing some boards and swaying in the wind a bit). What would these other treatments have done for me, besides creating some toxic side effects and disease resistance to drugs?
They might have made me feel better for awhile, with a normal lymphocyte count and no nodes to look at in the mirror. (This emotional high might have continued until I began to relapse, which is when the sudden realization that I had fewer treatment choices ahead of me might have hit me on the head, causing a Homer Simpson-like response, namely “D’oh!”)
They would have “bought me time” that, it turns out, I have purchased at a much cheaper cost.
(Indeed, since marrow impaction has not been an issue for me up to this point, I am amazed that chemo has been pushed at me as much as it has. How much of that was quality thinking on the part of my doctors, how much of it was a reflex action?)
Have I taken a risk by not getting a thorough housecleaning of lymphocytes from my system by chemotherapy, by barely holding my CLL in check (if that) by using a low-tox, rather ineffective agent?
Yes, but it is a small risk compared to chemotherapy. Strange complications from untreated (or minimally-treated) CLL can and do happen, but they are uncommon. For example, Dr. Lippencot’s fear that a lymph node would cut off a bile duct to a kidney is, it turns out, almost all hat and no cattle. But I did finally hear, last year, about a case where this happened. (The patient had chemo and his kidney was saved.) So allowing a lot of disease to mill around the body has its risks. Another one is clonal evolution -- doing nothing can still net you a 17p deletion, for example. But there's no reason to increase your chances of such an occurrence if you don't have to.
And the fact is, chemo increases the likelihood of a whole lot of bad mojo. The negatives of chemotherapy and precipitous treatment have been reported, demonstrated, and nailed-down. Is it worth risking burned bridges, a 17p deletion, Richter’s Transformation, pneumonia, rampant autoimmune disorders, pulmonary failure, and God knows what else unless one absolutely has to?
Alternate universe me says “no.”
And so, on Monday, I return to my hem/onc for a routine visit and no doubt a routine discussion of when to again use boring old Rituxan, which gives half-assed remissions but allows me to keep my whole ass intact.
I have been thinking about Rituxan dosing of late, and it seems like nobody knows what the optimal dosage is and what the optimal frequency of dosage is. You’ve got Dr. John Byrd with his 375 mg/m2 three times a week for four weeks and you’ve got Dr. Ron Taylor and his low-dose 30 mg injections. You’ve got doctors who want to do Rituxan maintenance of 375 mg for four weeks every six months or when a patient’s lymphocyte count reaches X number or when Jupiter aligns with Mars; and doctors who do one infusion a month, or every three months. Multiply the number of doctors treating CLL by the number of patients treated and you have as many variables as there are when it comes to Rituxan dosing.
Marilyn and I bought a handmade objet d’art at a thrift store once. It’s called a “mood barometer” and looks a bit like a clock and has two hands, one that says “He” and one that says “She.” The hands can be pointed to any number of semi-amusing places, including “Just a dear,” “Grumpy,” “Ooh-la-la,” and “Hysterical.” (We’ve had them on “Hysterical” for years now.)
I am tempted to make one for Rituxan, with one hand that can be spun. It will land on one of the various dosing choices, and I will go to Dr. Belle and say: “Let’s try this one next time.”
Of course, I am not really skilled at carpentry and I have already experienced some of the dosing variations. But I have not tried low-dose, or regularly-scheduled dosing every three months or six months. I will discuss these options with Dr. Belle, as well as possibly adding steroids to reduce the bothersome pelvic nodes for awhile. I will do some kind of Rituxan treatment in the not too distant future. And I will have my annual FISH test.
And, if the Fates and the FDA allow, I will finally stop using Rituxan at the end of this year or sometime the next.
I will start using HuMax-CD20 instead.
I've go to admit it's getting better: More good news about my CLL (chronic lymphocytic leukemia) - Most of my blog posts can be followed here. The full story of my CAR-T therapy, the incredible rollercoaster and the amazing results can be found there I...
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