Dr. Furman on genomic testing and MRD negativity in CLL (chronic lymphocytic leukemia)

I am going on radio silence and am writing this from the airport in Qatar so please don’t be upset or worried if I don’t respond to questions or comments.

Betsy Dennison, an oncology RN and NP who handles our website will be posting some interviews from ASH and EHA while I am gone. Today she put up this pretty cool one with Dr. Furman  that really explains the different types of genomic testing and the changing importance  of MRD-  in the era of new therapies.

I must admit for a world traveler, this trip to photo safari in Kenya has me worried. It is a long way aways and it is a long time gone in a poor and dangerous country  in some areas with all kinds of disease that are not a concern here

Once I am there, all should be well. I hear that at the tented safari camps, all is calm and secure if still noisy from all  the nearby animals.

Clothes are sprayed with permethrin, I have a ton of DEET and it is not mosquito season.  I will take Malarone. Kenya does not require a yellow fever vaccine  and risk is very very low and Typhoid can be given as a killed vaccine.  

I am staying away from salads and fruit drinks- that will be hard, and bringing a ton of emergency meds (cipro, immodium, Z-Pak, prednisone, pain meds, anti-histamines, suture kit, disinfectants, and an extra week of all my daily meds including my ibrutinib.)  Sunscreen, N95 masks and hand-sanitizer too.

And I won’t feed the lions, or monkeys or swim with the hippos.

I look forward to catching up when I return.

This is the first trip in years where CLL has not been at the top of the agenda, and where internet is iffy at best.

Stay strong.

We are all in this together.

Brian

Short and Sweet News: Less CLL (chronic lymphocytic leukemia) cells in my blood than 90 days ago

Good news. 

The absolute number of my B cells where my cancer lives dropped by almost 1/5 in the last 3 months from 246 to 216 after slowly climbing over the last year and 1/2. 

This is a very welcome and somewhat unexpected finding.

I am planning on it being the start of a new trend in the right direction.

4 plus years on PCI-32765 AKA ibrutinib and counting. 

Only time will tell if my resistant sub-clone and with it my CLL is truly shrinking, but the climb has stopped and that is reason to be celebrate.

The Patients' Perspective on the Changes in CLL (chronic lymphocytic leukemia) Treatment from EHA

If you recall, a month ago I was in Copenhagen for the European Hematology Association  (EHA) meeting and I had the privilege to be asked to speak with a very distinguished panel of CLL experts at a symposium that drew over 1,000 hematologists. Recently in our Conference Coverage section, we have posted a video review by Dr. George Follows of that symposium. You can hear about the highlights here. http://cllsociety.org/2016/07/panel-discussion-management-cll-changing/

Presenting the results of the 350 patients who answered our survey on therapy really added to my credibility in front of my fellow doctors. Thanks to those who helped with that.

If you were on vacation during these first weeks of July, we’d like to call your attention to our quarterly newsletter The CLL Tribune and also request that you take 3 minutes to answer our latest short Reader Poll about what you look for in your CLL physicians. You can access it here. https://asktellq22016.questionpro.com/ Thanks to the 140 CLL patients who have already responded. It really helps. The Tribune is the product of many authors, both patients and doctors. Please enjoy the articles and interviews from the Q2 2016 issue of The CLL Tribune:

· Reading/viewing an interview with Dr. Jeff Jones about Venetoclax from the recent EHA meeting in Copenhagen in Conference Coverage

· Read answers to reader questions by Dr. Rick Furman in Ask the Doctor

· Learn about what bone marrow does in The Basics Section

· In Beyond the Basics, find out about the ASCO sponsored TAPUR trial which is looking for new creative uses for already approved targeted therapies

· Learn new facts about CLL in the Did You Know section

· View some data from our most recent Reader Poll and share with us your opinions on CLL experts and whom you might recommend to other patients in our Ask & Tell section

· In Living Well with CLL, you can read about:

o Why You Should See a CLL Specialist

o How my Support Group Saved my Life

o I Don’t Have CLL. Yes, I Do. Now, I Don’t.

o On Being a Novice Patient

o May I Remember Never To Forget

In the meantime….

Stay strong.

We are all in this together.

Brian Koffman, MD

Volunteer Medical Director of the CLL Society

7/16/16

http://cllsociety.org

CLL Tribune: Our 4th Chronic Lymphocytic Leukemia Newsletter with Articles by CLL Patients and Doctors

Last week we published the 4th edition of The CLL Tribune. We’re so grateful to the patients and physicians and others who share their experience and expertise to enrich our CLL Society community. If you would like to share your story, or have ideas for future articles, please reach out to us. 

This week we would again like to highlight the content from our quarterly newsletter and also request that you take 5 minutes to answer our latest Reader Poll about what you look for in your CLL physicians. You can access it here. https://asktellq22016.questionpro.com/

Please enjoy the articles and interviews from the Q2 2016 issue of The CLL Tribune: http://www.cllsociety.org/newsletter/ 

• Reading/viewing an interview with Dr. Jeff Jones about Venetoclax from the recent EHA meeting in Copenhagen in Conference Coverage
• Read answers to reader questions by Dr. Rick Furman in Ask the Doctor
• Learn about what bone marrow does in The Basics Section
• In Beyond the Basics, find out about the ASCO sponsored TAPUR trial which is looking for new creative uses for already approved targeted therapies
• Learn new facts about CLL in the Did You Know section
• View some data from our most recent Reader Poll and share with us your opinions on CLL experts and whom you might recommend to other patients in our Ask & Tell section
• In Living Well with CLL, you can read about:

• o Why You Should See a CLL Specialist
• o How my Support Group Saved my Life
• o I Don’t Have CLL. Yes, I Do. Now, I Don’t.
• o On Being a Novice Patient
• o May I Remember Never To Forget

End of an Era

A Mythical Magical Mix of Creatures: A Chimera

Today I learned that my chimerism test in my peripheral blood was 100% host and 0% donor.

This test measure the percentage of my blood cells that are from me and from Yaakov who generously gave his hematopoietic stem cells in a effort to cure my cancer a little over 8 years ago.

While this result was hardly a surprise as my last test over 6 years ago and done from my bone marrow was 3% donor and 0% of the important T cells.

And we all knew that sadly my transplant failed years ago precisely because I rejected the graft.

Now it is clearly documented that I am no longer chimeric. Remember that a chimera is a mix of two animals- a lion and a snake and hawk as a mythical example.

I am just me- not a trace of Yaakov in my bloodstream.

Some 8 years ago, I was, for a brief hopeful few months, both Brian and Yaakov, hoping to become 100% Yaakov in my blood, with the real chance that his healthy immune system would kill on my cancer forever. That I would be cured.

Sadly, that was not to be and I lost the graft and relapsed. That story and my subsequent challenges in controlling my CLL is the genesis and the guts of this blog.

Now that era is officially closed. I did the test as there are some cases of donor chimerism climbing when patients take ibrutinib. Not me. Probably because I  already was at zero donor when I started on PCI-3275 (AKA ibrutinib) 4 years ago.

The news makes me a tiny bit sad. It reminds of a more optimistic time when I thought I might be able to forever say goodbye to CLL. While I still harbor that hope, it is tempered with heavy dose of realism.

I will be forever grateful to Yaakov for his generous and selfless gift of a chance to save to my life. And offer me a window of such hope.
SaveSave

Mixed Messages and the Sound of Distant Train Whistles

"I swear that too great a lucidity is a disease, a true, full-fledged disease."

NOTES from UNDERGROUND
By Fyodor Dostoevsky

Sometimes the ability to see around the corners into the dark or hear the distant train whistle when the railroads cars are still five stations away can create as many problems as these enhanced abilities promise to solve.

Case in point: 

My flow cytometry that looks for the clones of B cells that are characteristic of CLL has shown a slow but relentless progression of my disease over the last 18 months, but they still have to look pretty hard to find any cancer cells in my blood.

My mutation testings that looks for changes in my cellular pathways that are proven and as yet unproven to make my CLL resistant to ibrutinib shows many mutations but the biggest concern was that they found a mutation in PLCɣ2:p.S707F in 4% of sequencing reads. This is known to confer resistance by turning on the BTK pathway downstream from where it is being blocked by ibrutinib, blunting its ability to block B- cell receptors (BCR) signaling and so in theory allowing the cancer to grow again.

All this genomic instability should send me running to discover my next magic bullet or as my friend Wayne Wells (WWW) says, at least carefully choose what safe stone in the raging river to jump to next.

But this story is not news. It has been unfolding at glacier pace with these changes occurring over more that 18 months.

And here is the punchline.

My CBC or complete blood count is normal. Completely normal. No anemia. Normal platelets. Normal white cells in all lines. Normal!

All my blood chemistries are normal. My uric acid is low.

Both my LDH and B2M, well known markers of tumor activity are low and getting lower.

And my absolute lymphocyte count is a measly 1.6 and isn't moving anywhere. 

And I have no enlarged palpable nodes.

It is hard to get worked up when you ALC is in the low range of normal and you have no enlarged nodes. I wouldn't quality as having CLL as a newly diagnosed patient. Not even close.

Maybe the run away CLL train is coming to wreak havoc at my home station in the future, but it ain't here yet and G-d willing, it may never arrive.

So I am enjoying my life. We are getting ready for the trip of lifetime, a photo safari in Kenya in a few weeks. One of the best aspect of this vacation is that I will be on radio silence for 3 weeks and there is no CLL angle to the travel. Just pleasure.

A few weeks later, I am off again, this time to Estoril, Portugal where I will lecture to the European School of Hematology in September on ensuring patients get the benefits of the breakthroughs in therapy.

Of course I am not ignoring these faint signs that the labs are telling me. 

I am not just traveling and burying my head in the sand. 

I am looking at my options, but there is no urgency. I would be lying if I said there wasn't  some worry, but I know I have time. And treatments only get better with time.

Here's my point:

If it wasn't for the fantastically sensitive and frequent monitoring that I get as part of a clinical trial patient of Dr. John Byrd at Ohio State, I would be blissful unaware of any possible storm clouds. 

Am I better off knowing that something bad might happen (or not),  sometime in the future and there is no clear present agreed action to be taken?

Or would I be better off not knowing and simply being thrilled with an ALC of 1.6 (end of the story), as would be the case if I was receiving my ibrutinib in the community?

Each of us will have a different answer to this question and there is no right or wrong approach.

For me, I want to know. The more data I have, the better quality decisions I can make. That is worth the slight pangs of hearing that plaintive distant train whistle.

Stay strong

We are all in this together

And please take a look at the CLL Society's latest newsletter. Great stuff from fellow patients and leading researchers.