Tuesday, June 01, 2010

At last, progress on the nodes

“Good news, everyone!”

Fans of Futurama and its doddering professor and sometime inventor Hubert J. Farnsworth will recognize that expression and know the voice that goes with it. If I may take a little more liberty in the style of the good professor:

“The Lenalidomide-Ofatumumab Leukemi-o-meter De-noder appears to be working!”

Not all of Farnsworth’s inventions pan out, of course -– and not all patients get good results with the Revlimid (lenalidomide) and Arzerra (ofatumumab) protocol that I’m on. In its
own way, the protocol is as chancy and experimental as Farnsworth’s inspirations often turn out to be in Matt Groening's sci-fi cartoon TV show.

More than one fellow CLLer has reported to me that our expert doctors, big names you’ve heard of, are intrigued by Revlimid but have no idea how it does what it does. (Farnsworthian indeed!)

For patients, of course, the bottom line is results. After struggling with Revlimid dosages, tumor flare, fatigue, and a rash during a three-month period and seeing very little progress, I have to admit that I was becoming a bit pessimistic. Even the Arzerra, an anti-CD20 monoclonal antibody -- supposedly better than Rituxan, to which I have responded in the past -- appeared to be a bust.

Like a mantra, I found myself repeating a fact to myself from one study: The median time to best response is 5.9 months. Or as a researcher with experience in Revlimid trials told a friend of mine: “If it doesn’t work within six or seven months, it’s not going to work on you.”

* * *

The last thing I expected was that progress would be sudden. But it has been, like turning on a light switch. I alluded to it in my last post, which was mainly concerned with a Revlimid-induced rash that I had developed.

In the week prior to my May 20 monthly Arzerra infusion, I had finally managed to get my Revlimid dose up to 10 mg daily, which is what the protocol calls for. This obviously raised the levels of the drug in my body (ergo the rash). I began to suspect some subtle progress on the nodes in my neck. On Thursday the 20th, I had 1000 mg of Arzerra. Over the next four or five days, the switch went on. I began losing weight, and my neck and abdomen showed visible progress.

But the best example of change was the nodal mass under my right arm. What had been a hard baseball-like thing (well, half a baseball) -– a number of nodes that had grown together -– simply fell apart. I can feel individual nodes there now, but they’re no longer connected.

I’m making an educated guess that this could be going on in the abdomen, which has slimmed down considerably. I’m still full of nodes, but the masses may be breaking apart as each node reduces in size. My neck is looking positively scrawny as a mass on the right side has undergone a similar fate.

Why the Arzerra chose that weekend to kick in, I don’t know. To give my body a break from the rash, I was off Revlimid from May 20 until the night of May 24. But levels of the drug, which had been building while I was managing 10 mg daily, had to have been high on May 20, the day of the Arzerra infusion. Revlimid is an immunomodulator and perhaps it had sufficiently started to change the microenvironment in which my CLL cells live and my immune system functions, creating a more advantageous environment for the Arzerra. That's only a guess. (If the experts don't know how it works, I don't think I'm going to figure it out.) Whether that modulation has do to with dosage levels or length of time used, I can’t know for sure, although it stands to reason that both are a factor and that dosage is important.

That’s why I am anxious to get to and stay at the optimal dose of 10 mg daily. We all respond differently to drugs and their dosages. A tiny dose of vincristine, which probably would have gone unnoticed in another patient, once gave me peripheral neuropathy for months. Claritin, the allergy medicine, doesn’t work for me at all at the recommended dose. If I exceed that dose and take two Claritin, it does work. So in the case of one drug I am more sensitive than average, in the case of the other I am less so.

Revlimid in CLL is still a work in progress. But studies tend to indicate, and my own anecdotal experience suggests, that the higher the dose of Revlimid on average, the better the response. I surmise that CLLers on Revlimid should be on as high a dose as they can tolerate, 10 mg being the limit recommended by the drug’s manufacturer, Celgene.

* * *

Meanwhile, back at the rash . . . To control the rash, I began taking 4 mg of dexamethasone every morning starting May 25. The plan was to do 10 mg of Revlimid every other day and use the steroid to control the rash, easing myself up to adding 5 mg and later 10 mg on the “off” day.

At first, the steroid would work for much of the day, the rash only starting to return to my belly at night. After about four days, it began to work better. I’m now taking 5 mg of Revlimid on the “off” day and the dex seems to be able to control the rash over a 24-hour cycle.  Another couple of goes at 10-5 and I’ll try 10-10; if the rash remains under control, then I’ll stop the steroid, perhaps reducing it to every other day at first.

* * *        

Since I am on a steroid now, that does bring up questions about what role it may or may not be playing in my node reduction.

First, it must be remembered that the cascade of progress began several days before the first little green steroid pill touched my lips.

Second, I have had a fair amount of experience with steroids during efforts to control my autoimmune hemolytic anemia (AIHA). Four mg of dex is a pretty minimal dose (equivalent to about 21 mg of methylprednisolone.) It’s nothing to sneeze at, but 4 mg, in the past, has done little in and of itself to reduce my nodes.

Now, since I’ve started taking it, the progress on my nodes has continued (albeit at a slower pace than the post-Arzerra burst). It’s possible that it is a coincidence, but it’s also possible that the dex is a contributing factor, working in synergy with the Arzerra (anti-CD20 monoclonal/steroid combinations are well-known in CLL treatment.)  Once I’m off of it -– hopefully, sometime in the next week to ten days  my body will be adapted to 10 mg of Revlimid daily without causing a rash -– I’ll be able to judge whether it has had any effect. Obviously, if the nodes come back a little, that might indicate that it has.

But the bottom line is that the underlying progress is a result of the OL (ofatumumab-lenalidomide) protocol. Why or how it suddenly decided to visibly work after three months is a Farnsworthian mystery. My advice to those starting Revlimd and Arzerra is to hold on, get ready for the long haul, and be aware that you may not see immediate results like you do with most treatments. That makes it a little counterintuitive and a little hard to take at times, but you might just be surprised one day. I certainly am.


George Lee said...

my father has been drinking herbal drink that is curing his cll. i created a blog about it at http://www.my-spicy-kimchi.blogspot.com/

maybe its useful to you. tq.

David Arenson said...

Your comment is a little off topic considering my post but I did take a look at your blog. "Cure" is not the same as "reduction in white count." The official definition of "cure" is ten years without any sign of the disease returning.

"My father is now taking 2 Leukeran pills a day while taking the herbal drink twice daily," you wrote.

It appears that the Leukeran (chlorambucil) has a lot to do with the progress he has made.

Lymphocyte count can go up and down for various reasons (treatment, infection, stress, etc.) What is important is how fast the count doubles, which may indicate that something is driving the disease.

This does not mean that there is no value in herbal remedies -- green tea's active component, EGCG, has been shown by the Mayo Clinic to help in CLL -- but none of these things has ever come close to curing the disease.

Anonymous said...

Thanks for this post. You help us all by writing detailed descriptions of your experience with Revlimid and Arzerra.
I'm glad you have had a response in the nodes, since it seems like it is harder to kill CLL in the nodes. Who knew thalidomide would someday be altered to become a meaningful cancer drug!
I'm glad your CLL is responding! Good news!
Barbara Massey

Anonymous said...

Nah, nah, I told you so!

Specifically, my post of May 11 read as follows:

"As always, fingers (and paws) are crossed for you, David. I think a quite likely scenario will be for you to show little response for some months, followed by a rapid and significant improvement. I look forward to that report."

I am even happier than usual about being right!

Biology seems especially prone to tipping-point phenomena.


Anonymous said...

Well this is good news. One hopes a further reduction in those pesky nodes is to come. As an aside, the starting dose for multiple myeloma is 25 mg of Revlimid/day (21 days on 7 off) and 40 mg of dexamethasone/week.
About 40% of the patients need dose reductions.

Chonette said...

David, I am so happy you are making progress, nodes are the harder thing to reduce, I know well, that was my problem.
Hope this treatment gives you a good lasting remission.
Best Regards

Anonymous said...

David: Had my semi-annual visit with my onc and posed the question of Rev+Humax+dex. He replied with two comments: a) the CLL community is just starting to look at the drug combinations with Rev and he thought the trio might be on somebody's 'must try someday' list, and b) the rev promotes T-cell activity whereas dex has the opposite effect so maybe it might be a bad combo. He is head of a trial using PCR plus rev long term consolidation so he has pretty good insight.
Regards, TomD

Anonymous said...

I am hoping that your nodes continue to melt away. I am not really sure if this is just Revlimid or a synergy of meds you are taking. I guess you don't really care as long as it keeps working! The Arzerra/Solumedrol treatment for Tom reduces his nodes but does not keep them reduced for very long. While Tom's nodes reduced on Revlimid/Rituximab trial, his BMB continued to progress as far as percentage of CLL cells in the marrow. But, we both know that Tom was highly allergic to Revlimid and Rituximab and had to stop.
I am so excited to read this great news! Sorry I missed the big day and am so late in replying!
Looking forward to more news like this from you--

Amanda Krzywonski said...

I'm touched by your blog posts and you will be in my prayers. I hope you find good treatment, there is something out there for you. God bless you!

Anonymous said...


I'm so happy you've found something that is working for you!

Being exhausted all the time is something that healthy people just don't seem to understand... I'm especially glad to see you writing that you're getting some energy back! That might just be even getter news than the fact that your nodes are shrinking.

Looking forward to much more good news, in the future!