Sunday, January 24, 2010

Treatment update: My new friend len

I suppose an update is in order. No news is good news when you have CLL, and I’ve had no news for awhile. Now I’m gearing up for treatment again, this time with lenalidomide, better known as Revlimid, also known as "len" for short.

All of last year’s treatments basically bought me stable disease. A CT scan comparison from January to September showed only marginal improvement in abdominal lymph nodes, which is where most of my 11q-deleted disease lives these days. Over time my CLL has become less leukemic, more nodal, and my blood lymphocyte count is practically normal.

I remain at Stage 2, for what it’s worth. When I’m not hemolysing due
to autoimmune hemolytic anemia (AIHA), my red blood count, hemoglobin and hematocrit remain well in the normal range for a man. I’ve not seen the slow decline in those counts that follow with progressing disease. Over six years my platelets have gradually dipped, settling now in the 120s. That’s just below what’s considered normal, absolutely high enough for full clotting function, something to note but not to worry over.

My latest FISH test -- I get one every year, and the results have a huge say in how I approach treatment -– still shows the 11q deletion only, on 31 out of 200 chromosomes. This is a monoallele deletion, which means the relevant bit is broken off of the long arm of one of the set of two chromosomes #11. A biallele deletion would mean that both of the chromosomes 11 have lost the ATM gene. So hey, I’ve still got one arm to hang paper with, it seems. (A cautionary note is worth inserting here: As we all should know by now, the FISH test doesn’t probe for all possible chromosomal abnormalities that may eventually prove important in CLL. No news is good news in my case, but it may not be all the news, if you know what I mean.)

So by some measures -– including how I feel on any given day -– I am just
sort of trucking along with this thing in neutral. But it ain’t quite so. There are those abdominal nodes remember, none over 5 cm, but a whole, whole lot of them. My B2M is 4.8, a little over the line MD Anderson sets (4.0) to divide between those with better disease and those with worse. For me, the action is taking place in the abdomen.

Plus I’ve got the AIHA, with its hemolysis shoe always waiting to
drop, a sign that CLL has gummed up immune function and still continues to do so. I also have squamous cell skin cancer issues. I've had two SCCs removed surgically since 2005, several actinic keratoses frozen off, and I am on far-too-intimate terms with a tube of Efudex. SCCs can be deadly serious in CLLers, whose T cell surveillance function is weakened, because it is T cell surveillance that helps keep those squamous cells in check. CLLer T cells take a hit because of the lowered immunity that accompanies disease progression, and they can further tank due to immunosuppressive therapy, notably fludarabine and Campath.

I haven’t had fludarabine or Campath, which brings us to the menu of choi
ces I now face:

Looking at all the data tells me that my disease is stable-ish but also growing, more or less behaving but capable of getting that much worse if I don’t atten
d to it. For years I attended to it with single-agent Rituxan, but AIHA changed that game and while Rituxan was clearing the blood the disease found other avenues for growth.

So attending to it for about the past two years has consisted of costlier therapy, RCD, or rituximab, cyclophosphamide and dexamethasone. A recent DEXA scan shows my bones are no worse than they were two years ago, marginally osteopenic here and there. But steroids are not a long-term solution. Cyclophosphamide has done me good so far, nailing hemolysis when it occurs, but it is a potentially mutagenic agent and one to which, if I’m like most other people, I will only develop disease resistance to over time.

So RCD as “maintenance” is not realistic, and “maintenance” to me now means something a lot tougher and potentially more problematic than single-agent Ritxa
n. I have come to the end of Easy Street and there’s a big sign there that says “Road Closed.”

* * *

So, what to do? Besides lenalidomide, or Revlimid, the FDA has approved o
fatumumab, aka Arzerra, aka HuMax-CD20, aka the Monoclonal Antibody Formerly Known as Prince, for use in CLL. This is the bigger, badder, fully humanized anti-CD20 antibody, none of that wussy mouse shit. For someone who has used Rituxan to the max, its presence represents a potential new lease on life, or at least on effectiveness.

And because of that, it is an important drug in my arsenal. I am not treating it the same way I treated Rituxan. Sure, I might get a year or two of stability out of it by using it as a single agent, but then what? I think it is wiser to save Arzerra for combination therapy, the good old FCA, when that becomes front-and-center my only choice.

Which it almost is at this point: FCA, followed by a transplant at relapse, the CLL end game. But enter lenalidomide, an immunomodulator drug that intrigues and mystifies the experts. Some interesting data came out of December’s ASH conference, including a report from MD Anderson, which ran a trial of Revlimid and Rituxan in relapsed patients.

How len seems to help some CLLers is explained succinctly in this online interview with Dr. Asher Chanan-Khan, “Mr. Revlimid” himself, who goes over all the highlights from ASH, including a discussion of len at the end.

When it works -– and it doesn’t work on everyone -– lenalidomide seems to have a way of rebalancing the immune system, weakening the CLL cells themselves and compromising the nurse-like cells that protect them. Len can improve T cell and NK cell function, actually get the immune system to go toe to toe with the CLL. It works on high-risk cytogenetics such as my 11q. And while you have to watch for low neutrophils and low platelets while on the drug -– not to mention tumor flare, rashes, fatig
ue, nausea, and so on –- it does not appear to have the potentially mutagenic, viral-reactivating, Richtersy transformative potential of immunosuppressive chemo.

And keep in mind, for someone with AIHA, the idea of restoring an equilibrium in the immune system is powerful catnip. I have it on the best authority that two transfusion-dependent, hemolysing AIHA patients were treated with Revlimid; in both cases the hemolysis resol
ved and one patient is still with us three years later, free of the AIHA curse.

That, plus some added squamous control, plus the prospect of making a dent against that abdominal bulk, makes Dave a potentially very happy man. Which, defined in CLL terms, means someone who is able to control his disease, possibly even weaken it, for a long period of time without really compromising future therapy choices.

So, it’s worth a try. My insurance has rejected it, of course. It costs $60 a day per pill times 365 days and the insurance won’t even give it to patents with multiple myeloma, for which it has FDA approval. But my hem/onc, who now runs her own kick-ass office with a bent on getting patients the care they need come hell or high water, is optimistic that I can qualify for assistance from the maker, Celgene. We’re waiting on that, and on a few other details –- is it better to do with or without Rituxan, for example? –- but I hope to start soon.

* * *

Here's hoping all of you are doing well in your struggles with CLL. Even more, here's hoping you're out there living your lives to the fullest. Nobody gets off this planet alive, whether it is CLL that takes you or something else. Don't die with your regrets intact. Get real and deal and rock and roll. You only go around once, and this is it. Punch cancer in the nose and kiss life on the face.


Anonymous said...

My suspicion is that you are probably closer to obtaining approval from Celgene's Revassist than you let on or you wouldn't have shared your thoughts.

I certainly hope that the path ahead is smooth and worthwhile.

I hope that you will share the details of your journey with us a bit more often in the months to come as many of us will be interested in your observations while following this route. Many of us have considered utilizing lenalidomide, but have held back because of the uncertainty of response tempered by the known side effects.

Best of luck!

David Arenson said...

Yes, once it gets going (fingers crossed) I will come by here with some reports on all the fun. Not your daily sort of "I awoke fatigued and spent most of my morning on the toilet" kind of stuff, but a little bit of the big picture as I begin to experience and see it and understand it myself.

Anonymous said...

Thanks for the post, David. I've been wondering, and hoping for the best. I'm encouraged by your report.

Denny Fried

Anonymous said...

I'm so glad to see your post! I'm sure there are many of us who were hoping for the best...

You didn't go into it, but I hope you and Marilyn were able to do something special for the holidays. You both deserve it.

soapy said...

Good luck with this David, I missed reading your posts.

Anonymous said...

Hi David

Glad to hear of something that's possibly good news on the horizon.... I've missed your posts too - let us know any updates.

In the meantime, happy 2010 - may it be a good one for all of us.

cheerio for now

Anonymous said...

From what I've read, Revlimid has not given very good responses in CLL patients, with a low complete remission rate and a low overall response rate.

I suggest you consider HDMP+R. UCSD is getting great responses out of this regime, with 100% response rates,and CR rates comparable to FCR (FCA may prove too toxic).

I think Revlimid is over-hyped for CLL. Those big, bad drug companies, you know.

David Arenson said...

I've written a fair amount about R+HDMP here and I've also had Rituxan with high doses of both MP and dex. R+HDMP might have been a good therapy for me back in 2006, when I went to see Dr. Castro at UCSD about it, but my track record with similar protocols from last year indicates it wouldn't be a great fit now.

Some things have changed in what I'm planning, and I hope to post an update this weekend or early next week. Lenalidomide is still in the game, but I'm adding another player.

sandy said...

Hi David,
I am very blessed to find your site.
I am a NEWBEE when it comes to CLL
I was recently diagnosed with this disease and am still in a denial stage or should i say letting it "soak in" to the fact that I have cancer.
It was recommended to me to stay off the web when it comes to this disease.
I believe that knoweledge is power so here i am.
I am only in stage ONE. But I am having a really hard time with fatique. A couple of years ago I was diagnosed with pernious anemia. I was giving invfusions to help with this problem. Now two years later they tell me that it is CLL
I just had all of the tests including the bone marrow biopsy
When i got the results I asked the dr. about my iron count because I have been always fatiqued. He said wait let me look. He said according to the bone marrow biopsy there was NO STAINABLE iron present. I went through the infusions again and am still fatiqued. I feel lost but reading your blog has helped me.
Any suggestions?

David Arenson said...

Hi, Sandy.

I'm glad my blog has been of some help. I remember what it was like after diagnosis, so I know what you're going through.

CLL fatigue can have nothing to do with anemia. It seems to be the product of some sort of interaction between CLL cells and the body, and it seems to vary among individuals for no reason.

Of course, fatigue can also result from anemia. But it is unusual in Stage 1. Anemia -- hemoglobin below 10 -- is considered a Stage 3 matter.

Even though you have CLL, iron deficiency could be related to another issue. So it is probably good to get a workup that looks for clues across a wide spectrum.

As you begin your CLL journey, you may also find it helpful to join a CLL discussion site. The CLL Forum ( is full of experienced, caring people who can help you along the way.

All the best,