Good News from OSU About my CLL ( Chronic Lymphocytic Leukemia)

It is no fun to travel on Thanksgiving weekend across the country to OSU, spending hours in busy airports full of long lines of irritable flyers, but I am know that I am one lucky patient and I am grateful for my good care and my good drugs, even if it means crossing 3 time zones and leaving sunny beachy California for cold and wet Columbus, Ohio.

When I started on my ibrutinib trial two and half years ago there was a definite buzz about this new oral med that might change everything.

Well the game has changed, or more accurately is changing, and it is only going to get better with new non-chemo combos and second and third generation kinase inhibitors and monoclonal antibodies  (mAbs) offering us more and more options.

We aren't there yet, but we are moving fast (but not fast enough for those of us who need answers now) in the direction of long term disease control. Cure is still elusive, but there is now an active area of research on curing CLL, sometime inconceivable a few years back.

I am an example of the early changes.

Before ibrutinib and idelalisib and ABT-199 and now the second generation kinase inhibitors and the new mAbs came along in trials, someone like me with a failed transplant and a clone of 17p deleted bad boys had fewer choices than a vegan at a Texas BBQ stand.

Now 30 months into my ibrutinib adventure, I have a boringly healthy blood chemistry, and a mundane CBC (complete blood count) with a normal numbers of my red blood cells, my neutrophils, my platelets, and an absolute lymphocyte count of only 1.04

If you dig deep enough with PCR or sensitive flow cytometry, I suspect my cancerous clone is still lurking in the less that one percent of my B cells that still carried the signs of being part of the nasty cancerous clone gang when checked three months ago at OSU.

But as I said much to happy about it. And many reasons to give thanks.

Now with my personal good results locked in for another three months until I return for my next OSU clinic visit, I am off to ASH 2014 to bring the broader good news and to push the CLL researchers and pharmaceutical industry no to take their foot off the gas until we have a cure for us all.

Let me know if you have any burning questions for the researchers at ASH.

Life is good.

Dr. Byrd: "We are at an incredibly exciting time for patients and their families with CLL (chronic lymphocytic leukemia)" Let's all bake a cake of cure.

Cake of Cure

OK team, we have taken the first giant step in this moon shot. We've safely landed in a new world of disease control with no chemo. Now get us home.

The real work is just beginning.

We need potent combos of these new wonder drugs to help us stay in the land of remission forever, get off the daily meds, and maybe, just maybe find our decades from now that we have been cured.

We need more trials, trials that use NO chemotherapy. Trials that use drugs from different pharmaceutical companies. Abbvie links with Infinity Pharmacyclics is already working with TG Therapeutics in a clinical trial.We need more of these alliances that break down commercial barriers for the benefit of the patients.

We need brave patients to volunteer. While all of this sound so positive, let's not forget that when Gilead ran a sensible and necessary trial combining its Syk inhibitor, GS-9973 and its better known PI3k inhibitor, idelalisib or Zydelig (click here for the abstract), they concluded: "Despite promising activity in CLL, the combination of GS-9973 and Idelalisib resulted in an unexpectedly high rate of pneumonitis and resulted in stopping dosing of the combination These data need to be considered when designing future investigations combining inhibitors of B cell receptor signaling."

So we can't take anything for granted. These trials need to be carefully designed and monitored. But they are our best path to a cure.

It demands patients and providers and industry and the FDA all fighting together to "bake a cake of cure" for  CLL.

I like it.

Please enjoy this upbeat and realistic one minute video of my doctor, Dr. John Byrd out of OSU.



More soon on ROR1 including an exciting new trial,  and also on challenging paper on new mathematical modeling of ibrutinib resistance.

Good times indeed. Let's have our cake (vegan of course) and eat it.

ASH 2012: Dr. Wierda and Practical Advice on CAR-T Trials

In part two and final part of my interview from ASH 2012 with Dr. Wierda from MD Anderson (please  see part one first to get oriented) talks about some of the practical issues, upcoming trials, and possible role of CAR-T in conjunction with the new TKIs (tryosine kinase inhibitors).

In effect, Dr. Wierda is painting a picture where a small molecule such as ibrutinib or idelalisib or ABT-199 or AVL-292 or others in the pipeline is being used to reduce the amount of disease (cytoreduction) and then adding CAR-T therapy instead of the riskier allogeneic transplant to get rid of the nagging residual disease that seems to be left by all these drugs, and with that two step chemo-free process  offering the real possibility of a cure for our CLL.

As he stated, this are still many active area of research. Here's some issues that are near and dear to me.

Why the small molecules seem to move so slowly at ridding the body of all traces of disease- maybe we are just not waiting long enough or maybe it doesn't matter? It doesn't seem to matter in many patients with CML treated with imatinib (Gleevec). Will it be the same with CLL?

Can CAR-T therapy replace allo-transplants and become a practical, affordable path to a cure? A one-two knock out punch?

What about the rare relapses in CAR-T therapy with the cancerous clonal evolving to express no CD-19 and thus are no longer targets for the the engineered T-cells?

What are the bridges to these new therapies while we are waiting for answers?

Let's here a surprisingly practical discussion with one of the doctors who is not only discussing but creating this new future.



Dr. Wierda had to run off after this segment, so there is no part 3.

But Drs. Furman and Wiestner still have important things to teach us from interviews at ASH 2012 that I will be posting soon.

Seven Years Ago Today CLL Entered My Life

Seven years ago my wife and I were happily planning the home wedding for my oldest daughter. Now that marriage has given us our number one granddaughter who applauds her own first time success at standing up. Today. It is so good to be alive. Seven years ago, odds were not looking so good that I would reach this day. I am one lucky soul.

Seven years ago, it started so innocently. Some lumps at the back of my neck at the hairline. Soft, mobile, not tender. The symbol for cancer is the crab, with its pincers grabbing and invading. A tenacious rough visitor who clings to its hard won territory and gets ready to expand its reach. This felt nothing like that. These were smooth and rubbery, but persistent. I was overdue for lab work so I ordered blood work on myself (one of the advantages of being a doctor)  including the usual lipid panel and blood chemistries and a CBC on September 7, 2005.

The next day, Sept 8, 2005, seven years ago today, rocked my world. I remember being happy that  my cholesterol was so good, and that my chemistries were are fine. What did that matter when my white count was way too high and it was all lymphocytes?

While it would be more than a week before the final diagnosis was confirmed, that day everything changed. A disease enters our life when we decide we have had enough of the worry or the uncertainty or the pain or the itch or the whatever. The limit of tolerance or the limit of anxiety has been exceeded and we need relief, but it comes with a price tag. We seek help. We consult a doctor who makes a diagnosis. Many of these labels,  a sprain or bronchitis or a migraine are temporary. Many are not. Professor Ian McWhinney, the father of family medicine in Canada, and one of my mentors laid the groundwork of this understanding about how a word, a disease comes to our lives. Some maladies are amorphous, nameless and usually evanescent. All the bad one ones have names. and if it is compounded, it's usually really bad. Get scared if it's three words long and the first word isn't benign.

My three letter monster, CLL or chronic lymphocytic leukemia has been my traveling companion since that fateful day seven years ago. No, that's not right, because more than once it has been the driver, grabbed the steering wheel and heading us over a cliff until I could wrench back control. The first time was when another three letter hitchhiker, ITP squeezed into the front seat and sent us careening towards the rocks over and over again.

Cancer patients talk about pre and post diagnosis as different universes, as an epic paradigm shifts  whether we want one or not . We talk about "the new normal". We talk about altered priorities, lost trivialities, and new imperatives.

A cancer diagnosis has the opportunity to be a crash course in everything.

I quoted before from the late great Gilda Radner who said about her cancer: If it wasn't for the downside, everyone would want it.

But what a downside! Let us be honest. It comes with the real risk of intractable pain, increasing disability, bankrupting expenses, unimaginable inconvenience and stolen time, overwhelming fatigue, annoying side effects, unknown fears and of course death too soon, too soon, too soon.

The upside too is amazing. Life becomes purposeful, more focused, more urgent, more timely. The junk melts away. New friends and challenges and interests and opportunities appear. A brave new world. A chance to make a difference, a chance to beat the odds, blaze new trails and drags others with us on the road to, dare. I say it, a cure.

It seems possible now. The accepted wisdom is that the only possible path to cure for CLL is a transplant. Maybe that is changing. My transplant failed, as it does for about half of those who go that route. And it kills and mains too many.

Maybe the ibrutinib or GS1101 or GA101 will buy me and others the time needed for the CLL gurus to perfect the CAR-T or the next winning cocktail to get us to the promised land of no more leukemia, forever.

Much has changed in the seven years since my diagnosis. Then they was no therapy even shown to slow down the disease or add a day to survival. Options were limited to toxic drug combos or  the go for broke transplant.

With my nasty mix of 11q deletion, complex karyotype, CD38+, elevated B2M. strongly positive ZAP 70, 100% unmutated, aggressive ITP, and the recent addition of the worst or the worst, 17p del, I have more than beaten the odds.

I should be long gone. But instead, I am feeling stronger than ever with less fatigue, with blood counts near normal and nodes that are getting harder to find.

Seven years out and I am charging ahead to see how I help more CLLers get the best possible care and push the scientists to not take their feet off the accelerator. We aren't there yet and our path is not yet clear, but we are closer and the palliative options are increasingly gentle and effective. This is all good.

Although there are no guarantees and everything could chance in a heartbeat, and moreover, G-d forbid, I don't wish to invite trouble through trumpeting my good fortune, but the truth is that seven years out and my life has never been better and my hopes for all us CLLers have never been higher.

I am so grateful to all of you who follow along here and elsewhere and who share your stories.

The best is yet to come. Please stay the course. Our future is bright.

My granddaughter stands up for the first time and applauds herself. Does it get any better.

I see where President Clinton stole my best line at the Democratic convention.

But I stole it first.

WE ARE ALL IN THIS TOGETHER.

What I want for CLL

Here is the guts of an email that I sent to a friend and to the SLL/CLL yahoo list serve about what I dream about for all of with CLL.

I would love if there was an option that provided a high probability of a cure even if it was fairly toxic such as existing therapy for testicular cancer and others. Go through the hell of chemo and be done with it, except of course for the constant looking over your shoulder to see if our nemesis is returning and the very real late risk of a secondary cancer, especially another blood cancer including MDS (myelodysplastic  syndrome) always looming. Still it's desirable not to need to stay on meds forever. The possibility of the cancer escaping control or late yet unknown side effects is too high and we are living with cancer, not post cancer.

What we have now (outside of clinical trials) is the worst of both worlds, namely toxic therapies that hold no promise of cure (except for the transplant lottery). Gentle long term control is clearly a much preferable and believable possibility based on the very early but promising results with the new kinase inhibitors and the BCR blockers. That is why we are both glad that we traveled to OSU for ibrutinib and others may feel the same for their choices of GS-1101 and different new pathway blockers.

Still we must insist that the researchers don't take their feet off the accelerator. We are still far from home and for too many of us, the hour is getting late. Control is a great start and a big move forward. I am happy and lucky and extraordinarily grateful to be part of that early trial cohort. Maybe it is enough. Maybe there is a magic cocktail out there yet to be proven that will kill the beast once and for all. Maybe when the disease is a long deep remission, it then will be possible to drive a stake through its heart with new chemo or CAR-T or some yet to be discovered chemical. 

What I do know for sure is that I want to live enough years to be part of the proof that our control paradigm has the legs for a long long long  hassle free remission or better yet, to see and experience all of us crossing the finishing line of a cure. 

We are moving in the right direction but I wish it was faster. I want a near future in which we will have the best of both worlds. a low toxicity, highly curative therapy. 

A major breakthrough in CLL therapy. There's a new serial killer in town.

They did it, they got the benefits of an allogenic transplant, namely a new population of T cells that alert the immune system in an ongoing way to search and destroy the cancerous B cells. A transplant sans transplant. The benefits without many of the most horrific risks.

Here's a link to a VIDEO that tells the story.

These T cells have been changed with the insertion of new genetic information by infection outside the body with an HIV type retrovirus that, when they are put back into the same patient, gives them the ability to recognize and attach to the CLL cells, to arouse a very robust inflammatory response (read that they initiate a killing frenzy of both cancerous and good B cells and its precursors), and most importantly to proliferate and stay around for at least a year.

Am I encouraged? You bet.

This has the potential to change everything. This has the real potential to cure CLL.

But at this point it all still potential and conjecture, and all therapies look great when they are brand new. There are may unknowns and concerns. Still, it is an exciting time to be a CLL patient.

More soon on what I think this means for anyone with CLL in general and for me in particular.

In the meantime, I am rooting for these new cops, this new "007" secret agents with their license to kill.

And all this was done with no pharma money!

Anyway you look at it, this is very good news.