Dr, Bill Wierda on the Importance of Clinical Trials in CLL

I’m home from the European Hematology Association Congress in Copenhagen. 

I received very positive feedback on my lecture and the preliminary data from our Reader Poll with many requests for more information. We plan to follow up with another survey, Seems the 1000 plus hematologists to whom I presented the data and the folks from industry really want to know what we patients think and want.

I attended several lectures on CLL, reviewed dozens of abstracts, and had some great interviews with world experts that I look forward to sharing with you in the near future. 

After the last long day, I finally got out of the convention center long enough to walk along the harbor and see the famous The Little Mermaid statue.

This week in the Clinical Trials/The Basics section of our website we’ve posted an interview with Dr. Bill Wierda of MDACC where we talked about the value of clinical trials and how he approaches the discussion with patients about joining a clinical trial. You can read a summary of our discussion and watch my interview with Dr. Wierda here. http://cllsociety.org/2016/06/dr-william-wierda-clinical-trials-cll-chronic-lymphocytic-leukemia/

In the meantime….

Stay strong.

We are all in this together.

Brian Koffman, MD

Volunteer Medical Director of the CLL Society

http://cllsociety.org

When Sportswriters Cover the Cancer Beat: The Uneven Reporting of the Bob McNair CLL (chronic lymphocytic leukemia) and Skin Cancer Story

The owners of the NFL team, the Texans, Bob McNair has come out and shared his successful battle with CLL and a very aggressive squamous cell (skin) cancer.  The newspapers in Texas were full of the good news, but they didn't quite get the CLL piece right.

Please take a look at this news report:

Texans owner McNair gets clean bill of health after cancer fight

Or check out:

Texans owner McNair healthy after 10-month cancer battle

where you will read:

"McNair's remarkable recovery has included ground-breaking experimental treatment for chronic lymphocytic leukemia (CLL)…"

I want some of whatever that is.

Here is my published comment in response to the article:

Good news. While Mr. McNair's skin cancer may be curable, not so with his blood cancer, CLL. At least not yet, however, it is often controllable with therapy. Since CLL weakens the immunity, it can make skin cancers more aggressive. The message here is that anyone with CLL and many other cancers needs to be particularly careful about their sun exposure and vigilant in checking their skin for any suspicious lesions. Sadly one cancer, especially CLL, can lead to another.

Turns out a few of the sportswriters got a bit scrambled in their understanding of the management of his slow moving CLL versus his aggressive skin cancer that spread well beyond the skin requiring extensive and repeated surgeries, radiation, chemotherapy and eventually skin grafting.

The press conference with Dr. Michael Keating out of MDACC (MD Anderson Cancer Center) tells a clearer story with the full transcript at this link. Dr. Keating has a long and broad view of what we CLL patients need and I am glad he is a leader on our Team CLL. I also love the way he can generated much needed publicity about our cancer that seems to spend most of its life in the shadows, avoiding the bright lights and headlines.

The ground-breaking experimental treatment mentioned in the report was pheresis or more commonly called apheresis and its experimental use is to increase our wimpy immune response and lower our high risk of secondary cancers and their reoccurrence. 

Dr. Keating explains it at the press conference:

"You’re all aware that there’s an increased instance of melanoma that occurs because of tanning beds and things like this, but the most common forms of skin cancers are Basil Cell cancer and Squamous Cell cancer and many people like Mr. McNair have more frequent visits to their dermatologists than to the other members of their families sometimes because they keep on coming back. So the one element of Chronic Lymphocytic Leukemia or CLL, which is the most common leukemia that we see in the western world, is that there is a complex suppression of the immune system and the only non-AFDA approved activity was part of an extension of a protocol where we could take immune cells out by a process called apheresis, where you go through a machine and you take white cells out and separate the immune cells and then stimulate them up a thousand fold so they go to one-hundred-million to one-hundred-billion and give them back and rebuild the immune system to try and prevent these events from occurring."

Looks as if the transcribers may have missed a few key words and phrases.

A few reflections on what we can learn from the news.

1: Another celebrity, Bob McNair, the owner of a proud NFL team, tells the world he has CLL and skin cancer. Of course I wish he had shared the CLL news earlier, perhaps even at the time of diagnosis in order to help remove the cancer stigma and demonstrate how well he continued to live his active life for many years post diagnosis. I recognize that sharing a cancer diagnosis is a complex and very personal decision. Still I wish he had told the world when he was in the battle and not after it was at least partially over, but still I am grateful for his thoughtful and generous comments to the media about his two cancers and the treatment. I have posted extensively on this subject and received many lively comments on the decision to share the news or shut up. This link will get get you started if you wanted to revisit that topic.

2: We CLL patients are all at heightened risks for skin cancers and even the usually well behaved ones can become very nasty with our suppressed immunity. We get more cancer and the cancers we get are more aggressive. We need to use our sunscreen and our hats and have a full body skin check (and that really means full body) at least once or twice a year. See this prior post on secondary cancer risk with CLL (and CT scans).

3: MDACC and others are working hard on ways to improve our immunity. We need that. Dr. Wierda talked about his immune boosting research last year in this post. Remember that it is secondary cancer and infections that kill the majority of us that arise as a result of our weakened immunity from the disease itself and its old school chemo treatments. No point of knocking the CLL back and then dying of a secondary problem.

4: Sportswriters should stick to covering sports. Or if not, get some help and fact checking. Many otherwise fine reporters when covering cancer go for the feel good story. I guess they get tired of writing about the bad news and dirty laundry the rest of the time. That's nice, but it is not the whole picture. I promise I won't write on sports (except maybe a little about my beloved LA Kings and ice hockey) if they won't write on CLL. You don't need a medical degree to be a good medical reporter, but it sure helps. If not, then please do your research or ask for help and please tell the whole story, the good and bad.

ASCO 2013: Dr. Wierda on Prognostic Factors in CLL (Chronic Lymphocytic Leukemia)

The whole arena of prognostic factors in CLL is constantly evolving, but a few principles have remained constant over the years.

1: Most, if not nearly all the data is retrospective.

2: Dr. Wierda and many others are refining algorithms that will weight the many variables to better predict our future including such helpful information as the expected time to first treatment or our chances of a durable remission or ultimately our chances to live long and prosper.

3: The markers predict for groups, not individuals, but that doesn't mean we should be therapeutic nihilist and ignore what our FISH tests tell us about what options improve our odds.

4: Bad prognostics are not in themselves an indication for treatment (outside a clinical trial).

5: Good prognostics doesn't always mean that our CLL will be a non-event.

6: New prognostic factors are being discovered all the time, but few will be of much clinical import.

Here is the second part of my interview with Dr. Wierda from ASCO 2013.

I will let him fill in the details on all these topics and other aspects of this moving target.

Again my thanks to  my friends at Patient Power for sharing the work and supporting the effort to get the important news about CLL from ASCO out and available to all those of us who need it to inform our choices about how we handle our disease. Check in on their website on a regular basis as Andrew Schorr is frequently update his informative site.



In fairness, I must add that other researchers have published data supporting a possible relationship between Notch1 and Richter's Transformation (or Syndrome),

I quote from a letter in the British Journal of Haematology, 2012, 158, 415–429


"NOTCH1 mutations were associated with a ~5·8-fold increase in the crude hazard of transformation into a clonally related RS (Richter's Syndrome) "

This is from an editorial from haematologica | 2012; 97(3)

"In fact, the first studies reported a high frequency of NOTCH1 mutations in .... disease progression towards transformation into Richter’s syndrome."

Now this is not the same level of evidence as in a full article, and as such might not pass mustard for Dr. Wierda and others as proof positive of the correlation, but it convinced me that it is worthy of further study.

There is just too much data out there for anyone of us to be aware of it all.

And that's OK.

ASCO 2013: Dr. Wierda Discusses Immune Therapies in CLL

In this first of several interviews from ASCO 2013, Dr. Bill Wierda of MDACC discusses immunity in general (or lack there of) in CLL and how that relates to the coming immune therapies.

He starts by explaining the basic difference between passive and active immune therapies.

His candid review of the trials so far points out the recurrent disappointments in the attempts to develop active immune therapies.

The story with passive immunity has had more success.

Monoclonal antibodies (mAb) such as rituximab or alemtuzumab were the pioneers of targeted immune therapy and have in many cases improved outcomes when added to chemotherapy without significantly increasing toxicity. Newer mAbs hold the promise of even deeper responses with few of the downsides of traditional chemotherapy and may even prove to work well without the addition of cytotoxic chemotherapy. Already useful examples include Rituximab and Revlimid or lenalidomide (R2) and the combo of HDMP (high dose methylprednisilone) + Ofatumumab. Powerful therapies with no chemo.

GA101 or obinutuzumab, a third generation anti CD20 mAB had received breakthrough status at the FDA and may be approved before the end of the year. The early data suggest this is both a potent and well tolerated treatment, hence the rush to get it to the clinic.

Passive immunity also includes the exciting CAR-T therapies that Dr. Wierda discusses. These are still in very early trials, but a few cases such as those out of U. Penn have seen spectacular saves when patients had all but ran out of all conventional options.

Immune modulating drugs (IMIDS) such as lenalidomide are in the early days of studies to figure out how they fit into the therapeutic landscape, but are clearly active in CLL and may improve some aspects of our impaired immunity,

This segues to another topic that gets Dr. Wierda really excited.

He tells of his research into ways to improve our immunity, to reconstitute our lost ability to fight off infections and to search and destroy the earliest microscopic cancers before they can grab hold and cause problems. Infections and secondary cancers are what kill those of us with CLL, and Dr. Wierda is fighting for ways not only to knock out our blood malignancy, but to also prevent us from dying not from our cancer itself, but from the damage the CLL (and its treatment) have already done to our ability to protect ourselves from infections and secondary malignancies.

This interview is from ASCO 2013 in June in Chicago.

It was great fun working with Andrew Schorr and the dedicated team from Patient Power in doing these interviews. I am grateful for their efforts and support and the willingness of the doctors to share their work at such a busy conference.

Look for more CLL interviews here over the next few weeks and keep checking Patient Power for other interviews that Andrew and I did on other cutting edge treatments for different cancers at ASCO in Chicago. Many of these have direct implications for how CLL may be treated in the future.

Here is Dr. Wierda:


Tomorrow it will be a full six weeks since my last IVIG infusion and blood draw. This is the longest I have gone without IVIG in the last six years and the longest I have gone without lab test since my first year with CLL.

I will report from the infusion center tomorrow.

ASH 2012: Dr. Bill Wierda on CAR-T Therapies and "Off the Shelf" T-Cells

Dr. Bill Wierda out of MD Anderson Cancer Center (MDACC) is doing important cutting edge immunological research in CLL and looking to improve and make CAR-T therapy a safer and more generic treatment option.

In the first part of my interview from ASH 2012, he explains how he is moving forward in engineering T- cells to target the CLL clone and spare the normal B-cells.

These are early days, but there is surely a vision of an exciting future that is becoming clearer and brighter. Think of these souped-up T-cells doing the work of an allogeneic transplant without all the associated risks. Imagine them seeking and destroying our cancer cells and passing harmlessly by our normal cells.

Dr. Wierda does not minimize the risks or the work left to be done, but the journey has begun. There have been startling successes at U. of Penn and MDACC and UCSD and collaborating on finding better targets to attack and quicker and cheaper ways to engineer these killing machines.

Take a look at my recent post with Dr. Kipps on ROR1 to set the stage.

This work is particularly important because since it was recorded, it has been revealed that some patients with CAR-T directed against CD19 are relapsing because the clone is losing its CD19. Clever nasty cancer.

Poor patients now not only have an aggressive CLL relapsing, they also have no B cells and next to none antibodies, probably forever.

More to come soon.

Exciting and promising and challenging times.

ASH 2012: 10 Minute Break from the Excitement of the End of the Chemotherapy Era in CLL

Since I last posted I have interviewed Dr. Wiestner and Byrd, two of the most important researchers in moving ibrutinib forward. I also taped a long discussion with Dr. Wierda about CAR-T therapy among other things. Dr. Furman who did the phase 1 ibrutinib trial is next, then meeting Dr. Jeff Sharman.

This afternoon more lectures on ibrutinib, lenalidomide, and the first one on CAR-T.

Squeeze in the poster sessions and exhibit halls. And a visit with my sister-in-law.

Let me just summarize the news from ASH on CLL. You may not have heard it here first, but let me shout it out loud and clear.

The days of chemotherapy for CLL are ending. 

Details to follow.