Dr. John Byrd, the CLL expert from Ohio State University in Columbus, had some interesting things to say in a recent telephone interview with the Leukemia and Lymphoma Society.
Byrd is one of my favorite CLL researchers because I think he calls it as he sees it and has good instincts about when and how to treat the disease. I say this not only as a patient who listens to his telephone and workshop comments, but also as someone who drove from Arizona to Ohio to see him for a second opinion and who knows several people who are patients of his.
Byrd, like another favorite of mine, Dr. Terry Hamblin, is a treatment conservative. Neither man seems to get caught up in the enthusiasm that prevails in places, namely MD Anderson, where some patients are led to believe that chemotherapy will cure their disease. (I am all for hope, but hope truly grounded in reality; speculative hope is an unkind cut to patients desperately seeking a way out of this box.)
Both Byrd and Hamblin are tethered to Earth by the logic of science, and in the reality of what CLL is, which means knowing how much progress we’ve made, but also knowing how much we don’t know. As Byrd told me, CLL is “a long journey.” It is for patients, and also for those who are working on ways to control and even cure it.
I recently caught up with Byrd’s June comments, which are in the form of a telephone education program called Current Progress in CLL Therapy and Clinical Trials. (There is now so much information available about chronic lymphocytic leukemia on the internet that one can start to suffer from chronic information overload. I am forever backed up in my reading.)
Byrd said some things that I found notable, and which show how thinking is changing and evolving. Reading the full transcript is well worth your while, but I have pulled out some of what I consider to be the highlights, including a surprise or two, here.
Bye-bye BMB (and CT)
The first thing that caught my eye is that the dreaded bone marrow biopsy, bane of many a patient, may be a thing of the past. Like many of you, I was given one, or subjected to one, or allowed to have the experience of coping with one, as a routine matter after diagnosis in 2003.
“We’re fortunate in that a variety of new molecular tests have come forward that really trump any advantage to the bone marrow biopsy showing useful information,” Byrd says.“ For most patients who come to see me initially with CLL, unless they have low blood counts or another reason that I would do the bone marrow biopsy, say I suspect an infection, generally we do not do a bone marrow biopsy at Ohio State. Most of the other CLL centers are moving towards this. Actually, the new NCI guidelines that will be coming forward likely within the next year or two are not going to advocate doing a bone marrow at diagnosis unless there’s another question to answer.”
I was also given a CT scan, and was threatened with having a CT scan monthly until I agreed to my first hem/onc’s demand that I undergo single-agent fludarabine. Hmm, monthly CT scans or finding a new doctor -- what to do, what to do . . . it was an easy choice. But I still know a lot of patients whose doctors insist on using the CT scan as a tool for routine tracking of the disease. Not Dr. Byrd:
“There may be an advantage in the future for CT scans in predicting how CLL is going to behave, but right now that’s really not established and it’s not a recommended test,” he said.
Prognostic tests and treatment time frames
How do you know how your CLL will behave? Byrd gave an overview of the prognostic tests he recommends, those things that trump the BMB, including FISH and IgVH mutational status. Much of this should be familiar to patients by now (see my sidebar at the right of this page, CLL Prognostics and Planning.)
What Byrd added of note, I thought, was an indication of the time frame that accompanies these test results. If your FISH test shows a 17p or 11q deletion, Byrd says “there is a 50% chance that at one year you’ll go on to require therapy. There is a very good chance that by three to five years virtually all the patients in that group will have to go on to therapy.”
As to IgVH mutational status, Byrd points out: “IgVH-unmutated CLL patients all eventually require therapy and the halfway point, where 50% of patients go on to therapy of 100, is about three years.”
So, as you can see, knowing those two pieces of information can give you an excellent idea of if and when you may need treatment. Unless you prefer the life of the ostrich, there is no excuse for not getting these tests done. (I should add here that Byrd finds value in the ZAP-70 test but cautions that it is “very unreliable” when done at commercial labs. My own experience, in which Quest Diagnostics had me as both positive and negative, bears this out.)
In summing up, Byrd says, “There are three things we do when we see somebody at Ohio State initially for their CLL to predict how their disease could behave in addition to an exam: clinical staging, looking at the red cells and the platelet counts; the interphase cytogenetics, or FISH; and the immunoglobulin gene mutational status. That helps pick patients whose disease is going to behave in a more aggressive manner versus a less aggressive manner.”
When to start treatment
Byrd gives an excellent rundown on the question of when to treat, including whether early intervention might be warranted in aggressive cases, as well as some of the complications that can accompany progressing disease. This alone is worth your reading the full transcript, but I will mention one highlight here.
As to the timing of treatment, he says (italics mine):
“Often patients are asymptomatic when they’re treated. They have big lymph nodes or lymph nodes that are increasing, but they’re not bothering the patient. Their white count is going up, but they don’t have any other symptoms of the disease. And therapy is recommended too early. I make that point because if you’re not having any symptoms from the CLL and you start treatment, treatment is likely going to make you symptomatic. We tend to be very conservative when we start treatment.”
A man after my own heart -- for the longer I deal with CLL, the more I think there is wisdom in the words of the American commander William Prescott, who said at the Battle of Bunker Hill (with apologies to my British friends): Don’t fire until you see the whites of their eyes.
Single-agent Rituxan v. fludarabine
I have been milking the single-agent Rituxan cow for nearly four years, to the point that it can barely moo anymore. One of the listeners asked Byrd about Rituxan maintenance, which I know a good deal about from experience. Here is his response:
“Unfortunately, there has not been a randomized study of maintenance rituximab in CLL after reduction of the CLL with chemotherapy. There is a study that I understand is going to be starting in Eastern Europe to look at this. The only data that exists for rituximab being given repetitively over a long period of time is a study that was done by Dr. Haynesworth (sic) in Tennessee. That study showed that giving four weekly doses of rituximab every six months for a period of two years resulted in a remission similar to that achieved by fludarabine.
“So my take on rituximab maintenance by itself for CLL is that it may add a little bit, but probably the biggest advantage for treating CLL is going to be giving rituximab in combination with other therapies. As a single agent it’s about as good as fludarabine as a single agent.”
Ahem. Did you notice that last comment? As a single agent, Rituxan is “about as good” as fludarabine?
Now there may be some who, in terms of the statistics about CRs and PRs and the like, will take issue with that statement. But I think Byrd is talking about the effect on balance, over time, on a person’s CLL as part of that long journey.
I wish I could bring this comment to my long-fired first hem/onc, Dr. Lippencot, who refused to hear the word “Rituxan” and who insisted on fludarabine, fludarabine, and more fludarabine. But if any of you are still out there, visiting local hem/oncs who have been hiding under a rock and who insist that you be treated with single-agent fludarabine, take notice: In the opinion of one of the world’s leading experts, it is no better than single-agent Rituxan.
Byrd says, as do all the experts and accurately so, that Rituxan works better in combination therapy than alone. Byrd also makes the point in his interview that your first treatment choice is your most important because it can give you the longest remission. Does this mean you should always go with the therapy that gives you the biggest bang?
That would be an interesting question to ask the doctor the next time he does an interview.
Personally, I think it depends on the type of CLL you have and how it is presenting itself. Your case may merit one of the combination therapies such as RF or RFC. But perhaps a gentler hand will suffice, and in those cases there is no reason not to consider using Rituxan alone, maybe with a pulse of steroids to reduce nodes: the question in CLL is not always what works best, but what, tailored to your situation, will work well enough while preserving options for the future. It was none other than Dr. Byrd who counseled me to save RFC for transplant preparation. CLL is a long journey, remember.
Transplant update and synopsis - DGA—Synopsis; very late, but a quick review of events surrounding my transplant. April 19, 2017 I am alive and, really, very well. This is very late. I had...
4 days ago