CLL Support Group on July 3, 2013 at 4 PM at the Moore Cancer Center

Please join me tomorrow at UCSD at 4 PM on the 2nd floor of the Moore Cancer Center in the "Commons" for my talk to the CLL support group based on my experience as a doctor turned patient dealing with cancer.

I plan to start with a brief overview of CLL, discussing in general terms diagnosis, lab tests, prognostic factors, symptoms, complications, management, and how treatment is changing. The last half of my talk will be about my personal experiences as a patient ending with my participation in OSU clinical trial with ibrutinib.

It will feature video clips from my interviews with Drs Kipps, Wiestner, Byrd and Pagel at past ASH meetings.

After my 45 minutes, we all have a chance to meet and exchange stories and information.

Hope you can make it.

Clonal Complexity and Prognosis

Nothing in CLL is simple. Or easy to understand. Or consistent.

And it turns out that the greater the complexity, the poorer the prognosis.

It appears that FISH is just the tip of the iceberg. FISH probes only what is programmed to probe. Very focused, very limited.

Massive whole gene sequencing (sponsored by grants from the National Human Genome Research Institute, National Cancer Institute, the Blavatnik Family Foundation, and National Institutes of Health) has discovered much more complexity . There are 9 mutated genes in 5 core signaling pathways namely: DNA damage repair and cell-cycle control (these are our old friends, TP53 or del 17p and ATM or del 11q), Notch signaling (newly discovered FBXW7, and the better known NOTCH1), inflammatory pathways (MYD88, DDX3X, MAPK1), and RNA splicing/processing (two new players, SF3B1, DDX3X).

What is important is that for the first time ever more than half of these of these were discovered in CLL.

In the CLL patients studied, SFB31 was the second most frequently mutated gene occurring in surprisingly high 15%. SFB31 mutations was primarily associated with del 11q (that includes me) cancer already known to have a poor prognosis. This same mutation in SFB31 is founded in myelodysplastic syndromes that is a well recognized and rightly feared complication of CLL and its treatment.

Just the presence of the SFB31 mutation in CLL is an independent predictor of poor prognosis. Just what we need: Another risk factor to worry about. You don't want a bad spliceosome messing up your RNA.

Here is a link to the article in NEJM . This same material has presented at ASH 2011.

I bring it up now, not to add more reasons to worry, but to point to the progress being made in understanding the complexities of the disease.

Remember that PCI-32765 (ibritinib) is a targeted therapy that works in blunting of some of the pro-survival or anti-apoptotic crosstalk done by the BCR or B cell receptor between the cancer clone and its micro-enviroment . This drug and its ilk were not possible without the help of the basic science that elucidated these pathways, their importance, and their possible aberrations.

The good news is that these new mutations are strong clues as to how the cancer develops and what might be new vulnerabilities to be exploited in emerging targeted pharmaceuticals.

I am still clearing up a backlog of news from ASH and important journals and will be bringing you more videos and news soon. There is so much new in CLL that it is near impossible to stay current and not feel overwhelmed. I will try to continue to clarify some of what I believe is the critical new stuff.

My treatment at OSU has taken more out of me than I anticipated, slowing me down, but I hope to up and more energetic and if the stars line up, bring you want I think will be even better news from ASCO.

CLL EDUCATION FOR PRIMARY CARE PROVIDERS

Friends

Here is a link to the first of several CME activities that I put together out of the video recording of my interviews of Drs. Kipps, Pagel, and Wiestner at ASH, 2011. I am hoping to do the same for ASCO 2012 in Chicago if I can get the funding support. Any ideas?

Please go to http://www.primaryissues.org/ and select the CLL recognition link. You need to answer the pretest questions to get to the videos and text.

There is much more to come, but these are a lot of work. I am pleased with how the first one turned out. My son, Ben was the camera man and did the hard work of all the editing.

I am committed to teaching primary care providers about blood cancers, especially CLL. I believe they can play a critical and unique role in the patient's care.

On a personal note, I am back from my screening visit to OSU and will be flying back Saturday to Columbus Ohio to start my weekly ofatumumab x 8 then and only then to I get to start my PCI-32765. My counts remain good, but my nodes are definitely on a slow upward march, so it will be good to get into therapy.

What is CLL? Dr. Adrian Wiestner from the NIH gives an answer.

This is pretty basic stuff for us experienced CLLers, but I think the clarity of the dual nature of CLL is particularly well presented.

It is a very short segment of a much longer interview at ASH 2011 with Dr. Adrian Wiestner who hails from the NIH and who has done and is doing very important research in CLL.

And is he is a great guy too.

Most primary care providers are clueless about CLL so I am putting together a program of videos and education programs to teach them how to better care for these patients. More to come.

Andrew Schorr interviewing me at ASH 2011

My friend and fellow CLLer, the Seattle based journalist Andrew Schorr does a great service to CLL patients in particular and many others with chronic illnesses in general with his helpful interviews with the major researchers, often at the big medical society meeting. Here he takes a break from the "usual suspects" and interviewed me at ASH. (The American Society of Hematology) , 2011.

Check out his wide ranging website full of real dialogue with doctors and patients at http://www.patientpower.info/ to learn more. I am sure you will.

Why I am keen on PCI-32765

This very nice blog post deals with the business as much as the scientific aspects of the enthusiasm about Bruton's Tyrosine Kinase (BTK) Inhibitors, specifically PCI-32765 in CLL and other B cell lymphomas.

It is a nice simple introduction to how the BTK inhibitors work and outlines the little but promising data presented at ASH 2011. The blog does not mention the 89% progression free survival in CLL.

I suspect we still don't have the whole story. In fact, I am sure we don't.

What do you think?

Am I and many others over excited about this little pill when the evidence is still pretty sparse?

Probably, but there doesn't seems to be much downside, and the other options of doing nothing or using an established therapy sure have their own very real problems.

And I can always move onto those options later if PCI-32765 doesn't work out. Moving in the other direction is not a likely option.

I am not going there. I have every reason to believe that I will be part of the vast group of dramatic responders, especially since my disease is so concentrated in my nodes and my 11q deletion has pretty much done everything by the book so far, which means my clone should melt away in this trial.

Can't wait to get started.

I see Dr. Kipps in three days to go over my bone marrow biopsy and get his final blessing on my plans.

Home from ASH

Finally home and ready to sleep after a long late meeting of our local CLL support group

Let me just say that the world of CLL is changing, and changing for the better.

Mechanistic understandings of what goes wrongs in the CLL clone and how to right it are starting to be translated from the bench to bedside.

Nothing is definite, but things look better than any time in the past.

More soon. I promise.

ASH Day 4

Yesterday was 13 hours of CLL, with a 1/2 break to discuss MDS.

I am heading home today with hope and information overload and sleep deprivation.

I will be posting some reviews of important sessions here soon, and after some editing, some audio and video over the next few weeks.

My friend Andy Schorr interviewed me as a patient/searcher and I will post that video later too.

But first I need to get home to my own raw food and some sleep.

Live from ASH ( Even Quicker interlude)

Looks as if the 11 q deletion is a much more complicated story than just ATM deletion.

This is good news and is one tiny step on the road to personalized therapy. More to come. Off to chat with Dr. Adrian Wiestner from the NIH.

Live from ASH (Quick interlude)

Before I rush off to 90 minutes covering several research papers with new data on the genetics of CLL, I thought I would share want will be a theme in upcoming post.

There is greater and greater light being shone on the misguided pathways in CLL. Messages to be fruitful and multiply and live a long life are heard loud and clear. Messages that you need to change your evil ways, that it is time to let a new and more healthy well rounded clone take over the real estate that you are hogging in your malignant old age, these messages fall on deaf ears (or actually on corrupted signaling pathways).

But there is hope to realign this failed process.as there are new targeted ways to unjam the circuits and turn up the volume.

Progress is being made.

Gotta run. Stay with me.

Live from ASH

So much to share- mostly very good news for those fighting CLL or with family and friends facing similar struggles.

The problem is trying to blog about the meeting during the actual meeting is similar to trying to text while playing hockey. Something is going to go wrong.

Makes me understand why people tweet.

I will have video, audio, and text to share. I am even being interviewed myself.

Let me me just tease you by sharing that this is a most promising time ever for CLL research.

Stay tuned. Stay strong.

We are all in this together.

Brian Koffman- your faithful cub reporter live from ASH 2011