Sunday, May 06, 2012

Hurry up and wait

Those of us with chronic lymphocytic leukemia are familiar with the concept of "watch and wait," which means being a patient patient while your disease take its course. This can involve a certain degree of dis-ease (pun intended) as you and your doctor lurk about, waiting for just the right moment to begin treatment, should that become necessary. 

Of late I feel like I've been experiencing something called "hurry up and wait," which is what you do when your disease definitely needs treatment but you are waiting for the best treatment option to make itself available, which is supposed to happen Any Day Now.

"Watch and wait" drives Type A personalities a little bit crazy, which isn't really a problem for me. "Hurry up and wait," on the other hand, can be a bit of a challenge.

In my case, since the end of the Revlimid era last November, the CLL has taken a turn for the worse, compounded by departing doctors, insurance runarounds, and potential clinical trials that have proven to be trials in more ways than one. I've written about some of this, and am here to provide a little update now.

The good news is that Any Day Now there should be an opening in a kinase inhibitor trial with my name on it. I've been waiting on two such choices for a while. 

The first, which I'll call Trial One, almost came to fruition six weeks ago. In fact, I was all dressed up for extensive testing for a trial slot, only to arrive and find I had no place to go. Seems an "adverse event" in the trial of said inhibitor had just raised a big red flag at corporate headquarters and further patient accrual was being put off. All this happened in real time as I sat in my hotel, or in the Vietnamese restaurant adjacent to my hotel. Eventually I was sent home with the knowledge that while Trial One was probably out for the forseeable future, there was a Trial Two that would have an opening in another month, give or take.

And, so, here I wait at home, far from pho, disappointed but cautiously optimistic that I might make it into the second trial, in which no adverse events have been reported to date, at least that I know of.

You could argue that I am lucky the adverse event in Trial One didn't happen to me. It was an unexpected case of severe tumor lysis, apparently, which means massive, immediate die-off of leukemia cells that, uncontrolled, can damage the kidneys. Trials are called trials for a reason, and as much as we like to think of ourselves as intelligent, forward-thinking patients, we are also in fact risk-taking lab rats when we sign on the dotted line. So maybe I dodged a bullet by not making it into Trial One, which would not have been so disappointing had the principal investigator not been so genuinely enthusiastic about its potential to help me.

Now, I could go into names of drugs and names of doctors here, but what I have heard is second-hand, and I'm not in the business of reporting such things as absolute fact. This is a blog, not journalism, and there is a huge difference between the two that I still hold somewhat sacred, having worked in the news business back when double-checking the facts counted for something.

To keep my CLL at bay while waiting for trials, I have been taking huge pulsed doses of steroids every few weeks. My new local hem/onc calls it the "myeloma dose" -- 40 mg of dexamethasone daily for four days. The advantage is that it does reduce the nodes temporarily, and it has bettered my platelets a bit (they're now at 101) while perhaps also keeping my hemoglobin steady in the low 9s, which isn't so awful once you get used to it. Plus the steroids leave your system in under six days, and the prophylactic meds (antibiotics, antivirals, antifungals) also leave quickly, meaning that you can be ready to qualify for a clinical trial without a long delay.

Since 2007, I've had a fair amount of experience with steroids, about which I plan to write at some point soon. I think they're a good but problematic stop-gap, and nothing more. Steroids are a potentially useful component in any "hurry up and wait" strategy, but they're no way to live.

The late Dr. Terry Hamblin once pointed out that in end-stage cases he would prescribe steroids once a month just to keep the patient going, and I can see how, when all else fails, it beats the alternative. 

Fortunately, we now have more alternatives, such as the kinase inhibitors, as well as Revlimid for those who can tolerate it, not to mention the supercharged T cells being studied at such places as the University of Pennsylvania.

Which brings us to the real game to win here. I call it "slow down and wait." By that I mean, allow science to outpace your CLL by just enough that it can save your life. I feel like I'm cutting it close on this one, but there really is no other choice, except to go marching off to the Relapsed-and-Refractory Factory and await the end.

Call me irresponsible, accuse me of "dithering" in the face of my own unplanned obsolescence, but I am not comfortable with following a conventional wisdom that can change from one day, or week, or month, to the next. In CLL, action can mean progress, but it can also mean the illusion of progress. Doing something just to do something may not always be the most rational course. So I often find myself taking my chances with inaction.

"Slow down and wait" involves a certain amount of powerlessness, of accepting things you probably cannot change, among them the possibility that Fate might throw something at you, for good or ill. By making wise (or just plain lucky) treatment choices you might be able to control the disease long enough to buy more time, but there are no guarantees, since the disease can always take a turn for the worse at a whim. As to the pace of scientific progress -- and the availability of its fruits in your locale -- that is all luck, pure and simple. 

So far, I've been fortunate that science has done more since my diagnosis in 2003 than I, or perhaps anyone else, might have expected. My disease behaved decently until last fall, and now has settled into a new plateau, worse than it was but not getting worse, at least yet.

And Any Day Now, well, I hope to be trying a new treatment that might just control this thing. So I'm hurrying up and waiting in order to slow down and wait some more. Welcome to CLL.


Anonymous said...

Is it soup yet...hope you get your portion very soon.

Was wondering what was up, so thanks for the update.

Anonymous said...

Thanks for finally writing an update. We worry out here in cyberland.
Hang in there, Dave. Praying for you and all the other bloggers that help us understand this disease.

Anonymous said...

I am an unwilling fellow member of the CLL club and have read your blog posts for awhile. I am relieved to hear that you are hanging in there. I wish you the very best in getting into the clinical trial that is best for you.

Anonymous said...

Echoing the above sentiment, I'm really glad you posted an update. I think about you and how you're holding up and am glad you've got a 'plateau' for now, and hope you get into the right trial that will make all the difference in the world for you. My husband was diagnosed with CLL (all the 'bad' markers) and is in the Lenolidamide trial for Stage I untreated and so far so good. My prayer is that you blogging for many, many more years. Please do keep us posted as we truly do care :)

David Arenson said...

Thank you all for your good wishes. I've been so busy with work that I've had little time for blogging or much else -- that's a good thing, on the one hand, but it does interfere with getting other things done.

Learning the art of patience and adapting to new and changing circumstances is part of the CLL experience. It really is a war of attrition, as Terry Hamblin once put it. I am reminded of World War I and the trench warfare that never seemed to end, with one side gaining a bit here or there, falling back and moving forward. I've fallen back of late, hope to regain lost ground later this year.

Anonymous said...

Thank you for the update! My husband has been through 1st round of FCR Lite, 2nd one coming next week.

stew (WORCESTER) UK said...

Hi Dave fingers crossed for the new trial i really hope it does the trick . I am on watch and worry , sorry thats watch and wait had my 3 month check in march "12" hematologist consultant, now on 6 monthly checks , diagnosed Aug "11" i asked when treatment did begin what was the alternative to FCR heard it can be very toxic on the body and have a increased (small) chance of changing the make up of the cll cells , the consultant said it was the" Gold star treatment at the moment" in the uk and "newest" . What do you think david ? sorry if already talked it about on previous blogs and appreciate you are busy and have your own worries at this time .
Best Wishes
Stew ( Student Nurse uk )

Anonymous said...

Thanks for the update, Dave. I've been on WW since 2006. I am a teacher, now retired, but in 2007 I had to leave the classroom because a room full of 10 year olds is a viral soup and I was catching everything brought into the room in triplicate. My lymphocytes are now over 125. IVIG therapy is keeping me healthy during cold/flu season but blood clots have become an issue. Thank God for warfarin and pradax.

Dave Eckberg said...

Hi Dave,

I've been checking in on your blog from time to time to see how you're doing. You and I are running rather parallel lives as I, too, have CLL and I, too, have a little blog I use to keep up with family and friends called my Adventures With Leukemia, though I readily admit that yours is better written and organized than mine.

I have had CLL for over ten years now, a landmark I never expected to see. My dad had the same disease and was dead within five years. I have had mostly good markers for most of my CLL ride; IgVh mutated, ZAP 70 negative, low CD38, low b2m and normal chromes. In the ten years I've been through a partial course of FCR in 2002, when I first got sick and my WBCs were doubling about every ten weeks; then in 2004 I had high dose CR in connection with an autologous stem cell collection (the usefulness of which can be debated)and in 2008 I had a course of FCR-Avastin (to try to knock out the nurse-like cells) when my WBCs got up to about 100K or so. That therapy made me transiently PCR negative for disease, which made me think I might actually be cured! But then, last summer, I found that I had finally developed the widow maker; the p53 mutation, the 17p deletion. Like you, I began developing masses in my neck and axillae. Last February I had a CT which showed numerous masses throughout my abdomen and pelvis, the largest of which was 8cms. By late March the largest had grown to 16cms, so rapidly was my disease progressing. We tried a course of Arzerra to try to hold the disease off for a bit, with initial success in reducing peripheral WBC counts and node sizes, but after about five months, it failed and my nodes began advancing again. I had rather hoped to get into a protocol with Revlimid but got into something better. At the end of March I started participating in a Phase 2 study of PCI 32765 with Rituxan. I'm hoping this is the drug for which you are awaiting a study slot. In my case, at least, the results of the PCI 32765 have been nothing short of astonishing. Within days of starting the drug combination I could feel a difference in how distended my belly was and within four weeks all the palpable masses in my neck and axillae were completely gone. I have now completed two months of therapy and am doing quite well. My platelets which were down to 70K are now back up to 91K and my hematocrit is back to about 38%, from 35 or so. I'll get another CT in about three weeks to see if the masses in my belly and pelvis have resolved but I can tell by the way I feel that they are either completely gone or at a minimum, greatly reduced in size. And there has been nothing of any consequence in terms of side effects so far; just some migratory joint pains, primarily in the small joints of my hands and feet. That is a very small price to pay for the results, at least in the very short term.

Well, after that prolonged introduction, let me ask the question which led me to write to you. Do you know which kinase inhibitor was used in the study in which the tumor lysis syndrome resulted? I'm curious, as I would have thought that might have been a problem for someone like me, with a large tumor burden at the onset of therapy. But, in fact, I had next to nothing in terms of side effects.

You are from the Phoenix area, are you not? If so, I believe there is a branch of the M. D. Anderson Center out there and I wondered if you were being seen there or not. Just curious.

And that's probably plenty for now. Bye now, and good luck with that study. Dave Eckberg, Denton, Texas

Dave Eckberg said...

Oh, yeah, if you care to get in touch via e-mail, my address is
Dave Eckberg

Anonymous said...

Hello again David

I don't know why but you've popped into my mind several times lately. It does sound like you've hit a rough patch...but I know you'll see it through. You seem to be good at that.

Anyway, I'll keep a good thought for you,hoping it works out with Trial two.

David Arenson said...

A couple of thoughts on some questions that have been raised:

Stew, from everything I can gather, it is indeed fair to say that FCR is the gold standard of treatment at the moment. And it does come with risks, as you point out. Nonetheless, it remains an option worth considering depending on the severity of clinical symptoms and results of tests such as FISH. I haven't had it but I would not rule out doing it if push comes to shove.

Dave, nice to hear from you. The study drug with the lysis problem was ABT-199. Apparently at one trial center, someone was give the drug without prophylactic allopurinol to protect the kidneys from tumor lysis, which is a kindergarten-level oncology mistake. The cell-kill was so rapid that the person had a real problem on their hands but survived. My understanding is that the first dose of ABT is now given in the hospital so TLS can be monitored. Apparently the stuff is so powerful it can work wonders overnight. I think there is good potential in the drug, although owing to circumstances I doubt I'll be trying it myself anytime soon.

I am waiting on another inhibitor with a better safety profile, although perhaps less dramatic results. I am told again, any day now.

These are all trials, of course, and things can and do go wrong as well as right.

MD Anderson has teamed up with Banner Health in the Phoenix area. They have a new, underutilized facility with its own small staff and no access to the trials going on in Houston, so there's not a lot of value in it for me. And guess whose insurance won't cover it anyway . . . For people in Arizona, I would suggest the Mayo Clinic in Scottsdale or the UA Cancer Center in Tucson as being the two best centers for care (and if you have to pay out of pocket, better to spend your money at one of those.)

Good luck to all. A luta continua, as they used to say in Mozambique.

Anonymous said...

HEY DAVID!!!!!! Glad to hear that you are too busy to post much! That's always a good thing in the World of CLL.

I'm sure you know that Tom has been on Ibrutinib now for a year and a is one amazing pill a day! Some side effects that are not published anywhere yet the research team on Ibrutinib will tell you that they have seen it in other trial rats. HMMMMMMMM..and why do they keep saying they are not seeing these? Tom's problem is purpura and itchy rash outbreaks monthly on his arms and face. Platelets at 115 but we have been told that all of them are not working properly. They show up on the blood test but it is like halloween. I may dress as a cop, but I don't know what to do as a cop in real life. (that kind of thing)---
Also, trending, falling RBC's. Perhaps there is an end point of Ibrutinib, but it has done the job this long for Tom. I love this treatment. Hope you get on it.
Next up for Tom----Well, the ROR1 CAR trial at MD Anderson. Possibly starting early winter or late fall. We will see.
Tell Marilyn HI and keep hanging tough, my friend.

Jenny LOU