Sunday, November 21, 2010

First, the good news

When last we left off on my Revlimid journey, I was planning to increase my dosage from 10 mg daily to 25.

The hope was that the higher dose would bring even more beneficial results, especially in terms of lymph node reduction. The plan was to increase the dose in two-week increments, as is done -– if the patient can tolerate it -– in a clinical trial at the leading center for Revlimid research, Roswell Park Cancer Institute in Buffalo, NY.   

All went well in the beginning. I did 15 mg for two weeks and then moved to 20. That lasted for four days, after which I was able to answer the question, “Why isn’t every CLL patient on 25 mg?” 

That’s also the “bad news” part of the story, which I will explain in detail soon. But first, there are some other things that deserve to be in the spotlight.

The big picture is that the more I use Revlimid, the more I am convinced of its usefulness. I’m in my ninth month of it, and despite the challenges involved in getting used to the drug and managing symptoms that arise, I have benefited greatly from it.  My autoimmune hemolytic anemia is gone, my blood counts are normal, and the lymph nodes are in retreat.

Tumor flare masks lymph node reduction

One thing I’ve had a hard time figuring out all along is whether the lymph nodes are reducing and by how much. You’ll recall that I had terrible tumor flare in the beginning. After doing the Revlimid Shuffle -– two steps forward and one step back -– my doctor and I  were able to calibrate the dosage so that the flare was no longer an issue. If it was there, it wasn't obvious.

Some time ago, when I was off Revlimid for five days, I noticed that my nodes got smaller. After I stopped 20 mg, I was off Revlimid for 16 days. The nodes again reduced, and kept on reducing over the entire period, which confirmed my earlier experience. This tells me that low-level tumor flare is continuous when I am on the drug, and that when I am off it the nodes recede toward their real baseline. (This is all good; tumor flare is generally considered to be evidence that the drug is working.)

To determine the actual progress I’ve made these past nine months, I would need to be off Revlimid for several weeks, after which I would need to undergo a CT scan to compare to the one I had when I started.

Since that’s not going to happen anytime soon, I am left with the second-best option, namely self-groping and educated guessing. By that measure -– and being conservative in my judgment -– I’d say the nodes are one-quarter to one-third smaller. 

As someone whose disease has become node-based over time, and who probably has more disease bulk that 99% of CLL Revlimidians out there, I cannot tell you how important it is to see such progress. 

And seeing is believing. You know you have CLL when you keep a folder of photos on your computer called "My Neck." Looking back at old photos, I can see that my neck is now as slim, on a consistent basis, as it was in 2004. The abdominal nodes are no doubt worse than they were in 2004, but I look less pregnant than I did nine months ago and have lost about 10 pounds since then. 

B2M test is a useful measure of whether Revlimid is working

Over the course of my 7-year CLL career, my B2M, or beta-2-microglobulin, has gradually risen. B2M is a protein shed by CLL cells into blood serum; the more CLL cells there are reproducing and dying, the more your disease is proliferating, the more B2M they put out. So, as a rule, the higher your B2M, the more active your disease. 

If your B2M is below 2.0, you’re considered to have “the good cancer” behaving itself. When your B2M gets past 4.0, MD Anderson says you have “the good cancer” behaving badly, which means you have less manageable, progressing disease.

Looking back on my case history, I think B2M has been an accurate measure. It was 2.2 at diagnosis in 2003, 3.0 by April 2005, 4.9 in January 2007. It has been lower, usually just after chemo has concluded and the disease is in some kind of remission. But in times of no treatment it has risen over the years, finally finding a plateau in the 4s since 2007. In June 2009, my last B2M before starting Revlimid, it was 4.5.

But there is a big caveat when it comes to B2M, During treatment, when tens of millions of CLL cells are being torn to pieces, that B2M protein can also increase in the blood. So in some cases, a high B2M is not cause for alarm. It’s a good sign.

Which brings us to August 30, when I had my first post-Revlimid B2M test. The result was a jaw-dropping 8.8. Things had been going so well. Did this test mean that the disease was progressing anyway?

After my two weeks of 15 mg and four days of 20, the B2M was 11.1. This is so high as to be almost laughable, if not also a little scary. But was it possible that the higher doses were causing more anti-disease activity, which was being reflected in the test?

Two weeks later, after I was on and off the drug and ultimately back on 10 mg, the test came out at 8.8 again.

All of which tells me that my B2M rose with treatment, increased with the higher dosages, then decreased when the dose did. At least in my case, the high B2M seems to be evidence that Revlimid is working, and is therefore jaw-dropping for a good reason.

Au revoir, Arzerra

My treatment began as the “OL Protocol,” modeled after one currently in trial at MD Anderson. The “O” is for ofatumumab, aka Arzerra. The “L” is for lenalidomide, aka Revlimid.  Arzerra is an anti-CD20 monoclonal antibody, much like Rituxan, perhaps better in some ways. MD Anderson had reported that patients treated with rituximab and Revlimid did somewhat better than patients treated with Revlimid alone.

But there has been debate about this all along. Revlimid appears to downregulate CD20 on the surface of B cells, which logically means that anti-CD20 monoclonals should have a harder time working when Revlimid is present. Alternate sequencing strategies –- say, have the Arzerra first, then do the Revlimid -– have been suggested as potentially being more effective. It’s important to remember that Revlimid is still new in CLL, its mechanism of action is not completely understood, and that we are in the trial-and-error phase.

Whatever the reason, except for one brief burst of node-reduction in May, the Arzerra never seemed to do much for me. Perhaps it’s because my CLL cells had little CD20 on them to begin with, which could be the result of using Rituxan over many years. Or maybe the stars weren’t aligned properly. Following my last Arzerra infusion in early September, my oncologist and I concluded that the Revlimid was doing the work and that the Arzerra was just expensive window dressing. So we’ve stopped it, and I’m on the “L” protocol now, which we are devising as we go along.

It appears that, so long as I can tolerate Revlimid and it continues to provide benefits that outweigh the risks -– more on that next time! –- I will be taking it for the foreseeable future.


Anonymous said...

Exactly what dose are you on now...15/mg daily without "rest" periods?

David Arenson said...

I'm on 5 mg and will probably go back up to 10 sometime soon. As I've indicated, there was a big bump in the road that I will write about next time. It required that I start low and go slow.

Anonymous said...

Glad to see the Good News!!

So do you think Revlimid will become a front line treatment by itself or somehow become part of FCR +R or PCO+ R?

Will Revlimid delay the need for heavy chemo extending the treatment clock?

Where do you think the journey will end?

Anonymous said...

Hi Dave
I like the name "Revlimidians". I think we should start a club or website for us.

Your friend and fellow Revlimidian

Dave W.

David Arenson said...

I think Revlimid has broad applications for all classes of patients: those being treated for the first time, those aiming to maintain remission after heavy-duty chemo, those who have become refractory to most treatment.

I'm in the latter group and I hope that Revlimid will act as a disease control for the foreseeable future. How long is that? Two years? Five years? Ten years? The rest of my life?

At the least, I hope it keeps me going until something better comes along (CAL-101?), with which it might even be able to be used in combination. And that this will eliminate the need to consider a transplant. If something like that could be accomplished in a patient with my markers and history, this would be a huge development in CLL.

If I were a patient looking for my first treatment, I would seriously consider Revlimid. Obviously, it could act as an effective disease control without many of the downsides of chemo, namely those involving severe immunosuppression and mutations to CLL cells, causing them to be harder to treat.

Time and data will tell, but Revlimid is probably going to leave the patient chemo naive, meaning FCR and the like would still be highly workable options as second-line therapy in case it fails. Revlimid does not work for everyone, and not everyone can tolerate its side effects.

The bottom line is that I'd rather take my chances with this than with FCR, which I know is going to fail in a few years. In a recent post I posed this question: Knowing what I know now, would I have made the same treatment choice in 2004? The choices then were FCR or single-agent Rituxan. I said I probably would have gone with FCR, although I have no regrets about choosing Rituxan and how it worked out. But had Revlimid been available, I would have chosen it. I think Revlimid is a game-changer.

Anonymous said...

Thanks for your thoughts, I wonder how many patients will be given an option to choose Revlimid as a first therapy option or directed to the F/PCR approach by "traditional" thinking?

Anonymous said...

It's good to hear that the Revlimid is working. I am going to have to start treatment very soon, and I also have 11q-deleted unmutated CLL, as well as bulky nodes, so I am going to be entering a trial that uses Revlimid, Thalidomide, and Rituxan. My goal is to keep the disease under control long enough for drugs like PCI-32765 or CAL-101 to become more readily available (as they seem to be even more significant game-changers than Revlimid) while still avoiding FCR.

Anonymous said...

Someone please tell me what I am missing. While we all certainly hope that drugs such as Cal-101 or the BTK inhibitors may prove to help a great deal where is the evidence that they are going to be game changers? Decrease of nodes to near normal in some patients does not a game changer make. I haven't seen any published evidence that they are particularly effective on the bone marrow. Am I missing something? For that matter, there really hasn't been much published yet to convince one that Revlimid (whether used alone or in combinations with rituximab, ofatumumab, thalidomide, etc) is necessarily a game changer.

I hope that I am wrong, but what am I missing? Please educate me & I'll be grateful.

David Arenson said...

The problem is, when your disease is progressing, you cannot afford to wait for all the data to come in. Seeing whether a drug is effective is an ongoing process; knowing for sure what is a game changer can take years and years if you want to truly nail it down. For example, FCR has been studied and studied but we still don't know what, if any, the survival advantage is over the long term compared to other therapies.

We patients are stuck making a lot of educated guesses on a playing field that is always changing. Two things are constantly evolving: 1) an individual's disease; and 2) researchers' understanding of the disease, from which we can better identify prognostic tests that have value and treatments that might be effective.

Save for treatments that have been around for decades (chlorambucil, cyclophosphamide, steroids) there is always a gamble involved in picking a course of action. When fludarabine came on the scene in the 1990s, studies showed it provided deeper remissions for more people than chlorambucil. But as time went on, we learned that F users did not have longer survival.

Which of today's new drugs will turn out to be disappointments, and which might truly be game changers? If you're around in 10 or 20 years, you might have the answer -- if you can afford to wait that long.

Anonymous said...'s me again. I agree with everything that you say, but I really do worry when people talk about unproven drugs as "game changers" when the published data show Cr and PR rates (albeit in heavily pretreated relapsed patients). When we begin to see results similar to what occurred with Gleevec during it's Phase I trials then we'll be talking about game changing drugs.

Anonymous said...

Is there any way to chat with you less publicly? I love your blog and would like to ask you some questions, but would like to do it without putting info out publicly. If it's possible, could you email me at

Thank you either way!! Thanks for sharing your journey and for thinking out loud with all the important details!!

Anonymous said...

"We patients are stuck making a lot of educated guesses on a playing field that is always changing. Two things are constantly evolving: 1) an individual's disease; and 2) researchers' understanding of the disease, from which we can better identify prognostic tests that have value and treatments that might be effective."

Very well put. We also have to deal with keeping up on the therapies out there in clinical trials if we want to make an informed decision. From what I have seen to date, relying on what my doctor advises would be a mistake, even if I wind up doing what he suggests. But at least these days we seem to have some things to chose from....

Anonymous said...

Cal-101 and the like can be game changers because they can (perhaps) stop the disease from progressing. I know one person who was on the short list for a transplant, who got in the Cal trial and has been pulled off the transplant list, at least for a while.

If one can significantly reduce the need for transplants, that would in fact be 'game-changing'.

Now if the FDA would just get moving...