Wednesday, December 12, 2018

Closing One Door, Opening Another.

December 10, 2018 was a monumental day for me. A huge transition.

After 38 years of caring for generations of patients as their family doctor, I retired today from direct patient care.

Bittersweet. Lots of hugs and more than a few tears.

It’s been a tremendous privilege to care for so many people, to touch so many lives.

Today, for example, I said goodbye to my 104-year-old patient, to another long time patient that I had helped decades ago out of downward spiral to reinvent herself, a married gay man who flew in from Houston to consult me one last time, a seventy-year-old who reminded me that I caught his cancer early and likely saved his life over 20 years ago, and a fellow leukemia patient that I helped with his hospitalization.

Family medicine threw me into the lives of blacks, whites, Latinos, Asians and others, newborns and the very elderly, nearly every religious group and agnostics and atheists, too, the fabulously rich and the desperately poor, the morbidly obese and the anorexic, those with poor health choices and health fanatics, many omnivores and a few fellow vegans, professional athletes, weekend warriors and couch potatoes, those with special needs, scientists and poets and painters, preachers and rabbis, musicians and dancers, lawyers and felons, students and teachers, fellow doctors, CEOs, factory workers, police and firemen, celebrities, the homeless and so many more.

I have dealt with the trivial and the deadly, often on the same day, often in the same hour.

I have shared the darkest and happiest moments in some of my patients’ lives.

I have shared birth and death, the latter, too often and too soon for so many.

I will miss all my patients dearly.

But I leave that incredible job that has so defined me for the last 4 decades to care for folks in a different way, to care for a cohort, to save lives through education, support, advocacy and research that I will be doing as I move to the CLL Society full time after 4 years of what was essentially a more than full time unpaid job.
I will now work for the CLL Society from 8:00a.m. to 6:00p.m., instead of from 8:00 p.m. to 2:00 a.m., and on the weekends.  More importantly, in accepting the position of Chief Medical Officer and Executive Vice-President of the nonprofit CLL Society, I will no longer have to divide my energy and will be able to focus solely on how to improve the lives of my fellow CLL patients.

2019 will be an amazing year. While many CLL issues remain unsolved, and we at the CLL Society will be directly addressing those through our research efforts, the biggest issue in the CLL world is not what should be done, but getting the message out to all the patients and their doctors about what are now proven to be the best treatments.

The problem is getting out the good news.

We have always said, “Smart Patients Get Smart Care.”™

We are now adding, “No Patient Left Behind.”

I will miss the one-on-one caring that has so defined me, but I hope to make an even bigger difference by improving the lives of all those who are touched by CLL.

Stay strong.

We are all in this together.

Brian Koffman

Thursday, November 29, 2018

Off to ASH 2018

Swamped so this will be quick, but I haven't forgotten the blog.

I am off to ASH 2018 where we are busy from 7 AM to 10 PM most days.

I go as a:

  1. Doctor to help my CLL patients
  2. Patient to help myself
  3. Reporter to bring the latest news
  4. Researcher presenting the largest ever survey of CLL patients to 30,000 hematologists
  5. Interviewer with all the top CLL investigators and friends from the nonprofit world
  6. Advocate to push for the right research and share the patient voice
  7. Interviewee as I am on camera myself several times answering questions about my journey an my research
  8. CMO of the nonprofit CLL Society looking for partnerships and support to keep our good work going
  9. Winner of one of the CURE 2018 CLL Heroes Award
  10. Friend catching up with so many of my pals from the CLL and blood cancer world of research, and advocacy
Much more during  after to report

Check out for the updates

Stay strong.

We are all in this together


Sunday, August 19, 2018

ASH 2017: Dr. Thomas Kipps on the ROR1 Antibody, Cirmtuzumab

At ASH 2017 held in December in Atlanta, Dr. Thomas Kipps from the Moore Cancer Center at UCSD in San Diego, CA talked about an exciting new target for very specifically killing off chronic lymphocytic leukemia cells while sparing normal cells, including normal B lymphocytes.
Dr. Kipps is one of the leading CLL researcher and has pioneered the work on a new antibody, cirmtuzumab that targets ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1).
Because ROR1 is found nearly exclusively on cancer cells, an antibody against it may be the holy grail of antibodies, one that hits only the cancer cells with few off target effects.
Take Aways:
  • ROR1 is an embryonic protein that may help the embryo develop new distant organs.
  • By birth it has largely disappeared from normal cells, but it can be found on the surface of many cancer cells including CLL cells.
  • ROR1 is involved in keeping CLL cells alive even when their B-cell receptor (BCR) is blocked by drugs such as ibrutinib.
  • Cirmtuzumab is an antibody against ROR1 that it very specific in hitting just that target.
  • Early studies used extremely low doses and it was only given four times.
  • Cirmtuzumab has proven to be safe in this phase 1 trial with no serious side effects including no significant infusion reactions.
  • The ROR1 antibody has a long half-life of 21 days.
  • While the early trial was for safety, there was clear evidence of efficacy in the few relapsed and refractory patients who received the higher doses of 1 mg per kilogram with a median progression free survival (PFS) of 259 days using that suboptimal dose.
  • The combination with ibrutinib appears to be result in higher kills rates of the chronic lymphocytic leukemia cells by blocking two separate signaling pathways necessary to keep the cells alive.
  • There are ongoing clinical trials looking at the combination of cirmtuzumab and ibrutinib. Here is a link:
  • While adding antibodies has historically not improved ibrutinib efficacy, cirmtuzumab is different in that it not just targeting a surface protein but is blocking a pro-survival pathway critical for CLL.
  • Cirmtuzumab also may be important in killing of cancer stem cells, which if proven, should reduce the risk of late relapses.
We have many exciting treatments for chronic lymphocytic leukemia, but cure is still elusive. It is still very early in the story, but he can sense Dr. Kipps’ excitement and his hope that cirmtuzumab, when used in smart combinations might be part of the mix that leads to what we all dream of, namely being able to say: I used to have CLL.
Here is my interview with my doctor, Dr. Thomas Kipps from UCSD. It’s 17 minutes, but Dr. Kipps is a great teacher.
For more of ROR1 and cancer stem cells, see this prior interview from ASH 2014 with Dr. Kipps.
Thanks for reading.
Stay strong.
We are all in this together

Friday, August 10, 2018

ASH 2017: Dr. Adrian Wiestner on Resistance Mechanism in CLL (chronic lymphocytic leukemia)

I had the opportunity to interview Dr. Adrian Wiestner from the National Institutes of Health at ASH 2017 in Atlanta GA about his and other researchers work on how CLL cells become resistant to ibrutinib and venetoclax.

Take Away Points:
  • Ibrutinib works so well in chronic lymphocytic leukemia because it blocks the B-cell receptors (BCR) by binding to Bruton’s Tyrosine Kinase (BTK). This blocking of the BCR leads to cell death.
  • About 7-8 out of 10 patients who become resistant to ibrutinib develop a mutation C481 that prevents it from it binding and thus fully blocking BCR, allowing the CLL to progress.
  • PCLƔ2 mutation is another cause of resistance as it turns back on the BCR pathway and gives a lifeline back to the chronic lymphocytic leukemia cells.
  • Cells with the PCLƔ2 mutation tends to grow more slowly and the CLL tends to clinically progress more slowly.
  • Notch1 mutation can be associated with early progression on ibrutinib which is often not CLL but instead Richter’s Transformation that carries a poor prognosis.
  • Many patients do well on ibrutinib who have a Notch1 mutation.
  • Richter’s is rare after the first year on ibrutinib suggesting that blocking B-cell signaling may block the stimulation that leads to Richter’s
  • Less is known about the mechanism of venetoclax resistance, but upregulation of MCL-1 might play a role.

While the numbers are small, we are starting to better understand the mechanisms of resistance for some but not nearly all patients who progress on ibrutinib. Our understanding of venetoclax resistance is much less mature. As this research develops, there is reason to be optimistic that we can develop drugs to overcome the resistance.

Here is my interview with Dr. Wiestner from ASH 2017 in snowy Atlanta Georgia:

Here are links to some of the research referenced by Dr. Wiestner

Here is more on resistance from Dr. Furman from our website.

Thanks for reading.

Stay strong

We are all in this together.

Brian Koffman

Sunday, August 5, 2018

He Did It


Stan Kurtz and his team, with help from so many of you, Did it. He swam the Catalina channel and raised his goal of over $25.000 for the CLL Society! Thanks to all who gave, but it's not too late to share in there joy. Consider a tax deductible (in the USA) got of $22, one dollar for each mile he swam in over 12 hours in the Pacific Ocean. Or more. It was an exhilarating and exhausting for Patty and me just being on the boat.

Now I need to get some sleep. 


SEE: The swim was on the local TV news. This will help us to do so much more for others dealing with CLL.

Lot's of pictures and videos on our and his FB page,

Stay strong.

We are all in this together.


Monday, July 2, 2018

10 years ago today I received my Transplant for my CLL (chronic lymphocytic leukemia)

July 1, 2008, Canada Day, was my first Day Zero- my first shot at a cure when after conditioning chemo-immunotherapy of FCR, I received my hematopoietic stem cells from an unrelated donor who I later discovered was from Israel.

The allogeneic HSCT didn't work- though the chemo gave me a short but deep remission. I never engrafted, and when I quickly relapse, my cancer was meaner, a 17p deletion had shown up and my chronic lymphocytic leukemia required a new approach.

The transplant did however buy me some time before I needed treatment again and the longer you wait, the better are the new options that are bee developed.

Fortunately my timing was great. When I couldn't put off therapy any longer, I was able to jump onto and ride a trial of ibrutinib, then called PCI-32765 in a phase 1B trial out of Ohio State University for seven great years and form many new friendships, especially that with Dr. John Byrd, my doctor at OSU.

When I could no longer ignore the fact that the ibrutinib had stopped working, that my CLL had mutated around it, I swung for the fences again, this time with a most experimental CAR T trial at the Seattle Cancer Care Alliance.

My second Day Zero was March 22, 2018 when I infused with my own generically modified T cells.

After a very, very rough course, documented in my CAR T blog, I am MRD (minimal residual disease) negative- I have no detectable CLL in my blood, my nodes or my marrow.

September will be 13 years since I was told that I had cancer. I should have been dead years ago, but I took risks that paid off, and as of today, I have the least leukemia on my body that I have ever had since diagnosis.

The extra time has allowed me to blog and establish the nonprofit CLL Society that is making a difference for thousands of CLL patients around the world.

I am one lucky guy and my future looks bright.

Monday, May 21, 2018

I've go to admit it's getting better: More good news about my CLL (chronic lymphocytic leukemia)

Most of my blog posts can be followed here.

The full story of my CAR-T therapy, the incredible rollercoaster and the amazing results can be found there 

I have been too slow to post good news, but let me share that my deep sequencing testing done on my bone marrow biopsy at day +28 post CAR-T showed no copies of the CLL DNA. I discuss what this means in more detail in my blog posts here:  My celebrations are detailed in the previous post.

Also on the CLL Society website proper is an interview with Dr. Dearden about combos in CLL ( they are the future for high risk patients) and other topics plus tomorrow we are posting Dr. Brown on bleeding concerns with ibrutinib. The news is reassuring.

Slowly getting back into the swing of things. Went to the San Francisco CLL Society support group yesterday and talked on the phone with the NYC group where Dr. Furman made a guest appearance to help answer questions.

Feeling stronger myself.

Stay strong.

We are all in this together.