ASH 2013: Dr. Adrian Wiestner Discusses Prognostic and Predictive Factors, the Nuances of 17p deletion and Residual Disease

Merry Christmas.

In the second part of the interview from ASH 2013 in New Orleans, Dr. Adrian Wiestner from the NIH gives us some very carefully considered reflections on the news from the cutting edge changes in our understanding of CLL.

I first asked him to revisit the important issue of predictive versus prognostic factors that I first discussed at iwCLL with Dr. Sharman.

His review of 17p deletion, particularly for those lucky few who are mutated with 17p is very hopeful and nuanced. Listen carefully.

Dr. Wiestner suggested a cut off of 25% to define high risk 17p deletion. The reality is that it depends. While Dr. Tam's research in Blood on de novo 17p del (from the time of diagnosis and not first appearing after treatment) find prognostic significance only when more than 25% of the nuclei are missing the small arm of one of the 17 chromosome, others suggests a lower cut of 20%, some 10%, and some as low as 5% in looking at all cases, de novo and acquired, of 17p deletion. Like many subjects in CLL, consensus is lacking.

My simple take is the less 17p, the better. None is the best.

And we all know that the less disease, the better. Dr. Wiestner points out the obvious but we we need to hear it: You have to get to MRD (minimal residual disease) negativity to get to cure. What does this mean for the new drugs that rarely seem to get to CR, let alone MRD negative? Dr. Wiestner shares some thoughts.

Keep in mind also that 17p is a bad player in that not only does it not allow apoptosis (cell suicide) in response to most chemotherapy and thus rendering common CLL drugs such as fludarabine and cytoxan most ineffective, it also allows the cancer cells to mutate (genomic instability) with no controls on a clone gone bad. Add this clonal devolution to a significant population of residual cancer cells and we begin to understand why initial responses to the new agents such as ibrutinib and idelalsib are excellent, but sadly late relapses are more likely in those of us with a deleted 17p.

This seems to me to be a strong call for dual therapy for the 17p population, but whether that is the answer will only be answered with clinical trials.

Let's listen to Dr Wiestner.



We are so lucky to have a team of doctors working to solve our issues.

More interviews soon.

ASH 2013: Dr. Wiestner Discusses Why Therapy in CLL Needs to be Individualized

In the first of my video interviews from ASH 2013, Dr. Wiestner of the NIH outlines in some detail just how heterogeneous a disease CLL is now understood to be.

Dr. Wiestner points out that the groundbreaking work of the late Dr. Hamblin on mutation status is now  much nuanced.

What this new understanding demands is a different approach for every patient based on their biology and their personal preferences.

This is a future that I can buy into.



I will be continuing to publish interviews from both iwCLL and ASH and share my take on some of the important ASH papers.

This short post is brought to your from the free internet offered at the Athens airport as I start my long trip home after meeting with some other blood cancers advocates in Athens, and having an amazing time enjoying new Greek friends and and ancient Greek sites.

More on both soon.

Life is good.

Paul Henderson Battles Back Against Cancer

Paul Henderson and me in Niagara Falls

Thank you, Toronto Sun for this good news story in your hockey section.

OK, I am still a Canadian.

OK, I am still a huge hockey fan.

OK, I still remember the goal he scored against the Soviets.

When we met in Niagara Falls in 2012 at CLLPAG conference, I suggested he look into the NIH trial for ibrutinib. At that time, I had not yet started ibrutinib, but was still in the ofatumumab stage of the clinical trial at OSU with Dr. John Byrd where I would eventually get ibrutinib and do so well.

I am glad to see he is having the extraordinary success that I and so many others are enjoying with ibrutinib and the other new medications for CLL.

I am moved but his spiritual response to his cancer challenge. Paul is a man of faith and this is the season of miracles.

I hope and pray that the cost of these medicines will not delay their access in Canada- in every province, for every patient that would benefit.

I salute Paul Henderson for getting on a plane and flying to Bethesda. Not everyone has the resources or the knowledge or guts to do that. Not everyone fits the admission criteria for a trial.

I want to build a CLL community where every patient across all borders has the opportunity for the best possible care.

I am traveling, having met with other blood cancer patient advocates in Greece, so I appreciate the Toronto Sun doing my work for me on this post. Little time to write here.

One comment:

The hockey great tells the truth when he says what we know is that ibrutinib will work for about two years, but that is only because that is the best data we have. Only a handful of patients have taken it for around 4 years now and nearly all of those are still cruising along with their disease controlled, but the truth is that most of the data is out about two years or less. The curves are very flat for the treatment naive (those whose first treatment is ibrutinib), meaning that nearly all do not develop resistance and are doing great. In the relapsed and refractory population, the great majority also continue to respond, but there is a slightly bigger drop off. There are clearly some late CLL relapses seen after a year or more on drug, mostly seen in those with genomic instability such as those of us with a deletion 17p. More on this with the exact statistics from the papers at ASH when I get back stateside.

When I get home, I promise that I will write more about the news about CLL from iwCLL and ASH.

But first this feel good article.

BY JOE WARMINGTON ,TORONTO SUN
FIRST POSTED: MONDAY, DECEMBER 16, 2013 09:50 PM EST | UPDATED: MONDAY, DECEMBER 16, 2013 10:48 PM EST
TORONTO - 

All Paul Henderson wanted for Christmas was a clean bill of health from his deadly cancer.
It was actually more his wife of 50 years, Eleanor, their three daughters — Heather, Jennifer and Jill — and seven grandkids who were doing the asking.

It was no secret it was wishing for a lot. A miracle may be more what they were praying for.

It was not looking promising.

Just a year ago, the thought that the legendary Canadian hockey hero, suffering from chronic lymphocytic leukemia, would even be around for another Christmas was a dream.
In a column on Henderson in 2012, he was open about his ongoing battle with a rare, often terminal, form of cancer.

“There are signs of it getting worse,” he told me. “I have to admit the tumours are not getting any smaller. The cancer is now in my stomach, chest and lymph nodes.”

He had dropped from 184 pounds to 160 pounds.

The man who scored the winning goal in the final three games of the 1972 Summit Series against the then mighty Soviet Union was running out of both time and options.

The only goal he was focused on was trying to stay alive.

But Henderson has been known to thrive in tough circumstances, including scoring the goal of the century with just 34 seconds remaining in the final game in Moscow.

More than 41-years removed, he has proved his flare of beating the odds once again.
“It’s either chemotherapy or a clinical trial,” he said in 2012.

He chose the clinical trial and with fingers crossed went down to Bethesda, Md.

“The tumour in my stomach was the size of a grapefruit,” said Henderson, who was at the Toronto Sun’s downtown offices for an appearance on Michael Coren’s Sun News Network show, The Arena. “My spleen was double the size and the tumours were all over my body including in my armpits and my lymph nodes were swollen.”

Enter an experimental drug, called Ibrutinib, which is now being referred to as “breakthrough” therapy. “I take two little pills in the morning.”

The tumours began to shrink and now while Henderson can’t say his cancer is in remission, it is as close to that as someone with his form of the disease can ever hope for. “In my bones, they said they were 87% affected and now it’s down to 5%,” he added. “And the tumour in my stomach that was the size of the grapefruit is all but gone.” He has put all his weight back on and is back to 184 pounds.

“I just feel great,” he said. “I feel terrific but I think it’s even better for my family.” Yes, Eleanor, the kids and grandkids’ prayers have been answered.

It’s a Christmas Miracle!

“The Lord be good,” was Don Cherry’s reaction.

Henderson said the good news is also that most of the people in his clinical trial have had similar results and that one day Canadians may be able to gain access to this yet-to-be approved treatment.

He is hopeful it could mean that chemotherapy could become a thing of the past.

“When people say it’s a miracle I just say I will wait until I get to heaven and ask,” teased a smiling and upbeat Henderson.

He feels fantastic and looks even better.

“My wife joked she wants to take some of those pills because they must have Botox in them,” he said.

The Hendersons are realistic that with cancer, every day is special.

“I am told that this drug will work, they think for two years, so we don’t know what is going to happen after that.”

But what he does know is Henderson is feeling positive about enjoying Christmas with his family and even his 71st birthday on Jan. 28.

“I feel blessed because my dad died at 49,” he said. “I have never been worried because when you have hope and peace, you can handle anything.”

Henderson said he wouldn’t change a thing.

“I think having the cancer allowed me to be able to freely talk about my faith,” he said.

And, this Christmas, he is also able to reflect on another remarkable do-or-die moment he pulled out from suspected defeat and turned into victory just in the nick of time. 

iwCLL 2013: Dr. Tom Kipps Discusses the Changing Role of Chemo-immunotherapy in CLL and the New Role of BCL-2 Blockers

Dr. Tom Kipps is my personal CLL physician and was announced the winner of the prestigious Binet-Rai award for his contribution to CLL research at the iwCLL 2013 meeting.

This interview from a few months ago provides important background to help understand and get perspective on the great news from ASH 2013 on ABT-199 that I will be reporting and analyzing here soon with the help of the many of the doctors who actually lead the research.

In the first part of this interview with Dr. Kipps in Cologne, Germany, he first lays out some of the groundwork of when not to use chemotherapy.

Next, he gives us some of the history of how BCL-2 blockers work. I love his cathedral and buttress analogy especially after walking through the beautiful and delicate cathedral in Cologne. It seems like only yesterday that I was there working at the iwCLL meeting and visiting the sights when I got a break.

Cologne Cathedral

Next he explains the risks of tumor lysis syndrome. Two deaths about a year ago that halted the trial for months. But it has restarted on was reported on at ASH.

And he touches us on the tricky area of how and when can we stop these meds.



Due to a technical glitch, the final part of Dr. Byrd's interview will have to wait.

I will be mixing videos and analysis from iwCLL and ASH over the next several weeks. So much to share.

ASH 2013: A Quick Perspective

After five frantic days of attending very detailed and jargon filled lectures full of the latest CLL news, reading hundreds of complex poster abstracts and discussing them with their authors, interviewing many CLL experts from around the world balancing their crazy schedule with the limited availability of space for the interviews, meeting with leukemia and lymphoma advocates from everywhere and forging new alliances, brainstorming with CLL experts about research design, shared decision making, and the patients' perspective, and talking with members of the pharmaceutical industry about supporting what I would envisions as the unmet needs for the CLL community, I am heading home with much hope and much to share.

This was an amazing ASH conference for those of with CLL. Expect surprisingly candid videos and challenging discussions.

I don't just ask the the easy questions. I am looking for signals that might hint at trouble down the line. I am not there to make the doctors or the drugs look good, but to dig for the truth. I am not there to throw a hanging curve ball, but to scorch a fastball on target and see how well it is handled.

That said, it was handled very well, and the for the most part, the drugs and the doctors, do look very good and the news for us is very exciting and full of promise.

So many positives, and a few cautionary tales to come.

More soon.

I will be posting several remaining videos from iwCLL, but I will be mixing in some of the new ASH stuff too.

But first, I need some rest and relaxation.

My respiratory infection is mostly but not completely gone.

Tonight will be my first chance to walk around the Quarter a little and maybe catch some Zydeco music. I can't leave NOLA sans laissez le bon temps rouler on Bourbon Street for at least for a few minutes.

iwCLL 2013: Dr. Byrd Discusses 17 p deletion with Ibutinib

I need to keep this brief. I am exhausted.

As my flight was canceled, I ended up on a red eye to Baton Rouge, then took a shuttle to NOLA.

Didn't even get to sleep much on the plane. There was a medical emergency in the row next to us so I offered my help. That kept me up.

All turned out well.

Back to iwCLL

In the second part of the interview with Dr. Byrd from Cologne, Germany for iwCLL  2013, we learn his ideas of how to approach patients with 17p deletion.

I am seeing a consensus growing that for the more high risk patients, monotherapy is probably not the way to go.

That said it is important to remember that all 17p were not created equally, and some, especially in mutated patients or those wit ha low percent of cells with the 17p deletion can follow a fairly benign course.

More on that later, but let's hear what Dr. Byrd has to say on the topic.


Though it was less than three months ago, it seems like so much has happened since.

ASH today was amazing. So much to share, with important papers and informative interviews. I want to dissect out a new treatment paradigm that Prof,. Hallek is promoting.

But first I will post most of the iwCLL stuff. It is too good not to share.

Still sick and bit hoarse from all the interviews, but I will survive.

ASH 2013: The Joys of Travel

What else could go wrong? Horrible respiratory infection (getting better), cracked computer screen (replaced), broken eyeglasses with a missing lens (found and repaired with one of those cheap kits you buy at check-out), and now our flight is canceled to NOLA for ASH 2013. Painful to have to cancel all the interviews that I had worked so hard to arrange, especially the very much in demand Professor Hallek. The best I could do after hours on hold has us arriving tomorrow morning on a pricy flight from LAX to Baton Rouge on a different airline. Then a long and expensive shuttle ride.

But I am busy texting and emailing and trying to reschedule what I can. And hopefully I can sleep a bit on the plane and shuttle.

Thankfully, most of the interviews don't start until tomorrow afternoon, but the rearranging means I may need to miss some of the lectures that I wanted to catch.

I can't do everything. Can't be everywhere at once.

I still expect ASH 2013 to be a stellar meeting for those of us with blood cancers, and I expect to be back in my stride by tomorrow.

This is all fixable stuff. No big deal. Minor annoyances. As those of us with cancer know too well, that is not something that we can always say.

Expect a brief update tomorrow, late.

iwCLL 2013: Dr. John Byrd Discusses the Role of Novel Therapies versus Standard Chemo-Immunotherapy

In the first part of my interview from iwCLL 2013 in Cologne, Germany, my doctor for my ibrutinib trial out of Ohio State (OSU) gives us his take on two of the pressing questions facing us patients.

First, what is the going forward role of chemo-immunotherapy?

Remember that FRC offers those with specific favorable markers a 60% chance of a greater than a nine years MRD negative survival. That is beginning to smell like a cure, but at what price?

Based on his experience with over 400 ibruitinb patients, listen to Dr. Byrd's take. He calls upon the experience with imatinib (Gleevec) in CML to illustrate his point. Not every agrees with Dr. Byrd, but I do.

Next I ask about the vexing issue of residual disease with these new agents. Dr. Byrd is not worried. Hear his reasoning.



On a personal note, I am off to a very frantic ASH meeting tomorrow. Expect on the fly updates.

Still sick and miserable, but I am not I will recover.  Coughing less with a normal chest and sinus x-rays More of a head cold now. I also have been hampered by a cracked computer screen and broken eyeglasses, but the show must go on.

iwCLL 2013: Dr. Jeff Sharman Discusses Richter's Transformation in CLL

In the final segment of my interview with Dr. Jeff Sharman discusses the dreaded complication of Richter's Transformation.

First he explains exactly what we are talking about and the importance of understanding the difference flavors of this sinister secondary blood cancer.

Why are we seeing more Richter's?

What is the future for those of with CLL?

Dr. Sharman was very generous with his time exploring these tough questions.

And I plan to prevail upon him again to update us from ASH next week.

But first I willing be posting many more interviews from iwCLL. So much news to share.

Here is Dr. Sharman. I so appreciate his making himself so available to the CLL community.



Personally, I saw my PCP today and he said my chest was clear. Great news. Still have a persistent cough, now dry and painful, but I am getting better. Voice is raspy, but I can talk, between coughs that is.

I am winning this battle will my allies of levaquin, cough meds, and pot after pot of a  hot tea made from mullein leaves, marshmallow roots, and slippery elm to sooth my weary throat.

iwCLL 2013: Dr. Jeff Sharman Discusses Two Issues: 17p deletion and Residual Disease in CLL

In Part 6 of my iwCLL 2013 interview with Dr. Sharman who has a lot of experience with several of the promising new CLL agents, we look at some more unknowns.

He reminds us about how thin and immature the data is when looking at 17p deleted patients treated with either idelalisib or ibrutinib, but, and it is a big but, how encouraging it is compare to the historical data. In other word, how much much better it is than standard therapy such as FCR.

Another take away message is when we are comparing studies, make certain we are comparing apples to apples. Results with treatment naive patients will be much better than that with a group of patients who had been a round the block a few times.

And sometimes the enemy of good is better. His advice is sound and I echo it. Most of these new drugs are a great leap forward in CLL therapy. At least for now when not one of the new oral meds is yet approved for CLL, don't be too picky about which one you can get. Do your homework, follow the literature (or my blog and other reliable online sources), check clinicaltrials.gov, and make the jump if appropriate.

Dr. Sharman also raises the question implicit in the observation that those treated earlier, before we are badly beaten up by chemo-immunotherapy or by the disease itself, do much better. Should we treat with these new agents earlier?  Only more trials will tell.

And he has an interesting historical take on the issue of the residual disease.

Here I might respectfully differ with the doctor. These drugs work so differently than traditional chemo or even monoclonal antibodies, that we may need to radically rethink our assumptions about what residual disease means in terms of prognosis.

I personally hope so. My next CT will be 21 months after I first swallowed a bruton tyrosine kinase inhibitor named at that time PCI-32765, soon better known as ibrutinib or now as Imbruvica. My nodes have changed little in the last few CT scans with gut nodes hanging around 4 centimeters, so the risks associated with residual disease are not a theoretical problem for yours truly. I may have reached my "maximum response", but maybe that is not such a bad thing. Again, only long term follow up with inform us.

Here is Dr. Sharman. Please see his other videos if you haven't already. Lots of good stuff in this segment.



Part 7 soon, and more interviews to come.

On a personal note, thank you all for your kind thoughts and prayers as I battle this nasty respiratory infection.

I think I have hit bottom, and am clearly getting better, albeit slowly with levaquin 500, a broad spectrum antibiotic, aboard. I am hardly well, but I am no longer getting worse. My fear of pneumonia is fading.