Back to Columbus while listening for Zebras

It has been wonderful not to get on a plane for a full 28 days, not that I don't love OSU or Columbus, Ohio.

Not that I have been free from medical care for the last month. Back at home, I did manage to stretch out my IVIG to 40 grams every 4 weeks and still have enough gamma-globulin aboard to keep my platelets coated and protected. I remain grateful to all those unknown donors that gave their blood to produce that precious pooled blood product. It was not that long ago I was in the infusion lab every two weeks to prevent a recurrence of my dreaded ITP. There are good reasons to believe that the ibrutinib may help to calm down some of my auto-immune dysfunction. 

I also saw my rheumatologists about my arthritic knees and muscle pains. He wants me to try PT and wearing my unloader brace. I'm down with that. My arthritis is much more of a day to day problem for me than my leukemia.

Dr. Sharma, my local hematologist and medical oncologist was consulted about my progress and what if any changes I should be considering. None. He was supportive from the get go of my going to OSU and is happy that the results have been so positive.

I had an appointment with my transplant doc, Steve Forman at City of Hope to bring him up date to date, and to get him thinking about, when, if ever, I might need a second transplant.  No commitment from Dr. Forman on that subject yet. He too is pleased with my response from the trial at OSU, but recognizes we are very early in the ibrutinib story. I also had him look at my slightly clogged left ear, now bugging me into its second week. One big disadvantage of being a doctor is that I can imagine all the possible terrible diagnoses that can cause unilateral congestion in someone immune suppressed such as me. Odds are it is nothing but minor congestion from a virus. Dr. Forman recommended Afrin and Sudafed for the flight so I can equalize. No antibiotics, no steroids, not dramatics. I want it to be gone so I can stop worrying about all the zebras (famous advice given to all medical students: When you hear hoof beats, you think of horses, not  zebras). All of with cancer walk the tight rope between being over vigilant and falsely blaming everything mundane on some nasty business related to our internal enemy and being nonchalant and thus missing the early warning of a possible storm brewing. 

Really for my local doctors, it more about me talking to them about the good news happening in Columbus, Ohio.

Tomorrow, I am on a plane again to pick up three more bottles of ibrutinib 140mg to last another 28 days and to be infused with 2,000 mg. of ofatumumab. I will be staying with new friends that I met when my wife and I met when were living in Ohio. The mid-west is like that - friendly. I am very lucky indeed.

I am not thrilled with all the packing, the long flights and the waits at the airports, not happy about another infusion of ofa that probably does little for my tumor burden, but certainly lowers my immunity and always raises the risk of an allergic or other adverse reaction. More blood draws and waiting around at the clinic. Less homey raw organic vegan food and sleeping in my own bed.

But it is all it is all worth it for my dose of my magic BTK inhibitor, ibrutinib.

From Bench to Bedside: My clinical Trial of Ibrutinib and Ofatumumab at OSU

I have just discovered an older online publication by OSU that nicely summarizes the design of my clinical trial.

I am in the third cohort that is described and I am doing fine, thank you.

The data from the first cohort was presented at the recent ASCO (the annual professional meeting for clinical oncologists) and send the stock of Pharmacyclics, the makers of ibrutinib, soaring because in this difficult to treat CLL population there was an unheard of 100% response rate. I will post again with more details and explanations soon.

For now however, OSU does such a nice job of explaining the rationale and details of their trial that I am going to let them do the work.

See: http://cancer.osu.edu/about/publications/frontiers/archive/2012/07/19/bench-to-bedside-7.aspx if you want to better understand what I am going through.

Giving my Veins a Rest. I've seen the Needle and the Damage Done

Ever since my low platelets appeared on the scene six years ago in my CLL battles, there has been very few weeks that I have not been poked or infused in one arm or the other often several times.

Except for the time of my transplant when I was having blood drawn four times a day and might have three or four infusions all hooked up at the same time, I have not a PICC (peripherally inserted central catheter) and I have never had a "port".

Here are my tips that I use for protecting my precious veins.

1: Showing up for any and all blood tests or cancer center appointments well hydrated and warm.
2: Regularly working my arms muscles with weights.
3: Applying pressure quickly and firmly for a few minutes when the the IV is withdrawn.
4: Following that with the compressive dressing COBAN for about another 30 minutes.
5: Most importantly asking for an experienced infusion nurse who gets no more than two tries before letting someone else have a go.

Over the last six years, I have received multiple therapies, at one time three infusions a week, and over the three months in Columbus for the Ibrutinib trial at OSU I got weekly ofatumumab infusions eight times. Add to that too many IVs for the contrast for my CT scans and too many blood draws, and it is a wonder my arms don't make look like those of a heroin addict.

This is another big advantage of the new small molecules- they can pass through the gut undamaged, so they are bioavailable orally. No more IVs. This isn't just more convenient. It is safer. It passes the control of our life saving meds and in some way of our cancer itself from the IV nurse and back to ourselves and our medicine cabinet at home.

My most constant companion over the last six years has not been rituximab or steroids, but the very precious IVIG for my ITP. When my platelet count dropped again the last time, Dr. Kipps recommended that I restart my IVIG but that this time I receive less each dose but get it more frequently, every two weeks, and I dutifully did just that for years. IVs every two weeks! I am now trying to stretch out that two week interval, not that I don't just love spending hours at the friendly infusion center more than twice a month. Not that I don't love having to plan every trip or vacation or appointment around the scheduling of my life saving protein elixir dripping into my veins. I am happy that it has worked so well and that I have access to such a precious and expensive product on a predictable basis. I am truly dependent on the kindness of strangers whose pooled blood product regularly coats my platelets and prevents their premature and dangerous destruction. It is true at so many levels that I am living in gratitude.

Today it was almost four weeks since any needles have pieced my skin, and my platelet counts remained stellar. My Hgb has climbed a bit (13.2), my white blood cells are prefect (8.2, diff pending), and my platelets are 363,000, a very safe and happy number.

And my veins are loving the time off.

Maybe it's a benefit of all the ofatumumab. Makes sense since rituximab helps ITP and they both target CD20+ cells. Maybe it is the ibrutinib reducing my disease burden, the driver of my distorted immune function, or maybe it is some direct effect the BTK blockage has on auto-immune function.

Once a month IVIG. Two more doses of ofatumumab.

A lifetime of cancer controlling pills?

This is a fine vision of my future.

No Cancer Connection

I had noticed a hard mobile non- tender nodule behind and below my right knee last week that I was not sure if it was new or not. Could it be a node?  A new tumor of the muscle or tendon? That could be bad.


So rather than self diagnose, I consulted an expert.


I saw my arthritis doctor who wasn't sure what it was at first. After an x-ray and an ultrasound it turns out to just be a calcified something or another, maybe a loose bit of cartilage that had probably escaped my joint years ago and migrated into the synovial cyst (Baker's cyst) at the back of my knee, a variation of synovial osteochondromatosis (SOC).


Anyway, it is always benign, not remotely related to my CLL, but caused by my arthritic knees from hockey and football.


Truth is that my osteoarthritis now affects my day to day life much more negatively than my CLL.


That is a good thing.


First I will fix my cancer, then I will replace my knees.


It's always something.

RULE 2 WHAT I HAVE LEARNED My Personal 10 Rules for Staying Alive

A while back I gave my first rule to live by if you have CLL.


Here is my second.


You have time, but you don’t have forever.


CLL is a chronic disease that gives us time to rub our chins, study our enemy, gather our allies, read about what has worked and what has not, check the wind, and plan our attack.


True, there are times when prompt action is called for, such as when I found myself bruised up with single digit platelets from ITP. I was on call for my group when I received an urgent call at home from my exchange that they had a critical lab level on Dr. Koffman. A few hours later I was in hospital getting IVIG and steroids, but that is another story. Moving fast may have saved my life. Similar stories abound for friends with critically low blood counts that needed urgent transfusions and others with serious infections that had to be treated stat. Some secondary tumors such as an aggressive breast cancer demand quick decisions and actions and take precedence over the more pokey CLL.


But these are the exceptions.


Most of the time CLL lets us move carefully, slowly and methodically. We should be prepared, but not usually preemptive and never rash. 


However, there are what Chaya Venkat and others call windows of opportunity that open and also shut.


It is like the stock market. The best time to have bought Apple stock was years ago, not after its big run -up.


Here are three common scenarios that demand we move with alacrity.


The first is financial.


1: 


Sadly pending insurance or job changes can force us to play our hand early. If we are going to be considering treatment in the near future but will have no insurance then, most of us would would not have the deep financial resources necessary to afford therapy. That is reason enough for some of us to move up treatment time.


The next is the most important, the most common and the most ignored.


2:


I tell anyone who will listen that the best time to treat your CLL is a month before you need to. Once our bone marrow is impacted and our counts are too low, many traditional therapies become much more problematic. Once our nodes are huge, many meds can not penetrate as well to get a complete remission and some such as alemtuzumab (Campath) are useless. Once we develop any new problems with our heart or our arteries and veins or our lungs or our kidneys or our even with our psyches, treatment can become much trickier. 


That's why it is important to keep a watch on the cancer. That is why a short lymphocyte doubling time is one of the agreed markers that says time to treat.


Today there may be a new reason to not delay taking action.


3:


Some of the new promising novel therapies such as ibrutinib and GS-1101 have limited openings in their trials, so if we are likely to need therapy soon, and want to have a shot at one of these new experimental agents, we need to watch what's happening with the trials at Clinicaltrials.gov, stay in touch with our support group locally or online and be prepare to move.


Still I would never recommend getting therapy that is not indicated just because an exciting trial is available now and won't be soon.


There is a cost to doing anything. 


There is also a cost to doing nothing.

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. 

The danger of getting advice from a non CLL expert

My search spiders, primed for anything CLLish, pointed me to a blog by a retired medical oncologist who shares with us his frustration with the limited therapies available for the many CLL patients he treated in the past and his excitement about finding an article reviewing new therapies.


I was pleased to read that an experienced seasoned general oncologist was turning his attention to our rare disease and was anxious to learn his insights.


I was soon disappointed.


He points out the realities when he practiced.


When I was in practice we didn’t have any very effective drugs. We had drugs that could eliminate most of the leukemia cells, but never cure the disease. Eventually, the leukemia would come back in spite of continuing treatment. So when I saw this article, I assumed that there were new treatments and drugs to offer these patients, because I had seen preliminary reports suggesting breakthroughs. Wrong! Yes many new drugs have been developed, but none are particularly effective. The only one that seems to be useful is a drug called Rituximab, which is an antibody directed against a molecule on the CLL surface. But even this drug saved only a few more people when it was added to standard treatment, treatment that is not much different than what I used. And in the key study where this was discovered, most of the patients were much younger than average.


 Later he concludes with this wet blanket for any fire we patients might have for the new therapies.


But for most patients, who are older and have active disease, a disappointment! No breakthroughs like the one for people with chronic myelocytic leukemia (see my article on Kareem and CML) where we have found drugs that are life-saving. Sorry.


What has he been reading? 


This is what happens when you have doctors who are not heavily involved in treating our disease. They may miss when the winds shift.  They are out of touch with the prevailing zeitgeist. 


They have been known to put their faith in gold standard across the board, whether appropriate or not. They too often rely on stale data, and they don't see the coming changes. Their care might be appropriate, compassionate, well meaning and competent, but it is not cutting edge. It is not the best that the present state of knowledge has to offer.


This oncologist blogger to his credit was making an effort, knows about the new prognostic markers, and warns us appropriately that none of the new therapies has yet been proven to extend life. He understands the disease, but doesn't see the import of the coming new therapies because he is not immersed in the research and patient care of CLL patients. He is waiting for the proof for the trials that show the new drugs will add years to our lives. 


That is a long wait, longer than some of have.


Here is what I wrote the doctor:


Contrary to your take, there has never been a more promising time for patients with CLL. Low toxicity  sea change therapies such as Ibrutinib, GS-1101 and other kinase inhibitors are entering phase III trials after extraordinary results in phase I and II trials. Lenilimamide, HDMP, ofatumumab, alemtuzumab, and bendamustine already ofter patients new alternatives for disease control and long symptom free remissions.  While I agree a trial that shows an advantage over the "gold standard" of FCR in survival is what we all want, it is unrealistic and unfair to ask patients to assume that all these game changing therapies will ultimately fail. I for one, like you am waiting for the proof, but I am very encouraged by the early data and like many patients with cancer, must make decisions with imperfect knowledge.


For a nice overview of the research on the new small molecules, please take a look at Blood June 19:
The B-cell receptor signaling pathway as a therapeutic target in CLL
Jennifer A. Woyach, Amy J. Johnson and John C. Byrd


Thanks


Brian Koffman MD -http://bkoffman.blogspot.com/


That is a great article that summarizes much of the recent research.  I recommend it


Truth is that the other blogger and I are both right. 


He is correct when he says that nothing is proven yet. CLL remains incurable for the most part. The best new therapies are just entering Phase III trials and that is a far cry from proving that will keep us alive a minute longer than placebo, let alone FCR.


But I am right too. Patients who were at the end of their therapeutic rope are seeing their lives extended. Patients too old or too sick or too refractory are being routinely salvaged with amazing consistency and minimal toxicity.


This is more than anecdotes. The reported data is getting stronger and stronger. The response rates and progression free survival numbers are to use a most non-medical term,  wonderful.


Could it all crash and burn in the phase III trial? Could every new drug and therapy in trial turn out to a loser? Of course that could happen. But that is not what I and many of my CLL friends and by the way, the smart money on Wall Street is betting. 


I think we got some winners here.


And I am not talking drugs or stocks or careers, but us patients. We are the winners if my vision of the future comes to pass. We will prove my colleague blogger wrong in his disappointment. And I think he will celebrate with us.


One final caveat. This well meaning clearly bright and thoughtful oncologist is out of the CLL loop. Make sure you doctor isn't also. That is why I beg you to get an opinion from a CLL maven. Picking the right team of doctors could save your life.

A Break from CLL and Wonderful Small Molecules to Share a Stanley Cup First

My labs were great today in muggy Columbus, Ohio. I am here for my monthly check-up at the end of my second cycle of ibrutinib and to receive another infusion of ofatumumab.  My mild anemia was stable. Otherwise only boring stuff on my CBC and even all the blood chemistries were normal. Nodes are continuing to get smaller and smaller. It's all good. The future looks bright.

Some insurance hassles with OSU, but I don't want to go there. It will pass.

I am writing my take on the role of transplant and the new tyrosine kinase inhibitors oral drugs in trials for an upcoming post, but right now I am taking a break from CLL (because I can- I am doing so well) to share this great photo that I think says it all.

Another Day in Paradise

Four Year Transplant Anniversary: A Request for your Help With CLL Research on Ibrutinib and More to Control and Cure CLL

I received this important email from John Byrd, my doctor at OSU, and one of the most innovative and patient friendly researchers in CLL in general and ibrutinib in particular. He is asking for your support in his fundraising efforts though Pelotonia.


Dr. Byrd is looking for ways to save lives without the risks and miseries of an allogeneic hematopoietic stem cell transplant or maybe even the use of the more toxic old school chemotherapy. 


In another email he said: The new trial that opened with Ibrutinib (Kami Maddocks PI) is being supported entirely by a 100,000 dollar grant from last years Pelotonia.  


He also wrote that the money raised is supporting the following studies that would not be happening without Pelotonia


1.  Post-doctoral fellow working on understanding role of autophagy in drug resistance in CLL
2.  PhD student working on an entirely new kinase inhibitor target for CLL 
3.  An idea grant from another lab (with us) looking at ATF3 as an immunosuppressive stromal factor in CLL


Four years ago today I had my transplant on Canada Day. It failed but I am still here.  Maybe it was a good thing that I never engrafted? I was spared the potential horrors of GVHD, but on the other hand maybe I would have been "cured" by now if it had taken. I will never know, but I do wonder.


Would I have made the same choice today with all the new options opening up?  The answer is probably not, but the data to help with that decision is far from being conclusive. We need to know more. It is so early in the research.


I am in the process of composing a post on the role of transplant in this nascent era of the new small molecules for CLL. It is an increasingly common question posed by patients and doctors alike.


If you can, please help Dr. Byrd and others in their research to get the answer to this and so many other cancer questions. Please consider clicking on the link to donate.


Thanks.


Please see Dr. Byrd's email below.


Dear Brian,

I am wrting to you because your help is needed.  I have decided to ride in Pelotonia and would greatly appreciate you to consider supporting me.  

Pelotonia is a grassroots bike tour with one goal: to end cancer. More than 10,000 supporters are expected to be a part of Pelotonia 12 on August 10-12, 2012. The ride will span two days and will cover as many as 180 miles. In its first three years, Pelotonia has attracted over 8,300 riders from 38 states, over 2,800 volunteers, hundreds of thousands of donors and raised $25.4 million for cancer research. In 2011 alone, a record $13.1 million was raised. Because operational expenses are covered by Pelotonia funding partners, 100% of every dollar raised is donated directly to life-saving cancer research at The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute. I am writing to ask you to help me raise funds for this incredible event. Large or small, every donation makes a difference.

What will your donation be used for?  The money derived from this race supports research to identify new drugs and also to perform clinical trials in cancer.  I am a leukemia doctor focused on curing a disease called chronic lymphocytic leukemia (CLL).  In the laboratory, Pelotonia is supporting idea grants to bring novel ideas that might translate into new therapies some day.  Additionally, it is supporting students and post-doctoral fellows to work on new antibodies (different from rituximab) and small molecules that could some day be therapies.  Addtionally, one of the trials that Pelotonia is supporting with money rasied from last year is with ibrutinib, a highly active bruton tyrosine kinase inhibitor that is very active in CLL.   We have seen this agent help many CLL patients and are delighted to have the support of Pelotonia to allow us how to use this medication better and along the way help patients with this disease.  Without Pelotonia, the trial with ibrutinib coul
d not happen.  I see Pelotonia as a way for us to move quicker to converting cancer to a chronic disease or one that is cured.   This is something I am passionate about supporting.  I hope you will contribute and remember no amount is too small.

When you follow the link below, you will find my personal rider profile and a simple and secure way to make any size donation you wish.

Think of this as a donation not to me, or Pelotonia, but directly to The OSUCCC-James to fund cancer research. Please consider supporting my effort and this great cause. My rider profile can be found at the following link: http://www.mypelotonia.org/riders_profile.jsp?MemberID=1227

Thanks for the support!

John