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.

Waiting for perfect knowledge?

It is always easy to tell when it is too late or too early to start therapy.

It is always easy (at least for me) to second guess any disease management decision.

It is never possible to get it all right and have all the facts.

So what to do?

For me, the answer has always been to get the best information and the best advice from the best people, and then act and stay mindful.

Some choices, such as a transplant, mean that you can't always be aware or mindful. You are just going to be too tired or too sick some of the time. That is where you need a well meshed team of loved ones to be your ombudsmen and of experts to execute the plan. These two groups will keep their eyes on different pieces of the puzzle, but they must communicate. This combo will give you the best chance to handle most of the inevitable bumps on the road so that you can keep moving forward.

Which brings me to another topic.

And another golden nugget:

If you don't know where you are going, you will never get there.

Assuming my chosen path of rituximab and cyclosporin continues to work its biological magic, and my nodes melt away not just where I and Dr. Kipps can palpate, but deep in the darkness of my mesentery, do I pull the trigger on a second transplant, a second shot at a cure and not just a remission?

That would mean a preliminary course of higher octane chemotherapy such as FCR or bendamustine with R or O to further reduce the disease burden and weaken my T cells so that I won't reject the graft as I did last time.

Or do I play out the string a little further in a different direction? Avoid tried and true chemotherapy and engage a newer sexier tango partner, such as one of the tyrosine kinase inhibitor in clinical trial now that doesn't promise a cure, but just a longer and gentler dance.

The risky cure or the unproven promise of a long deep remission?

There is a yet another saying in medicine. This one speaks to the appeal of a new medication.

Better use a new drug soon while it still works.

Is this too cynical an approach? Weren't all medications newborns at some time?

Some "new" drugs (triptans) have grown to be old and trusted friends and other (DES) have been run off leaving behind a trail of shame and tragedy. Some (Penicillin G) have been mostly pushed aside by the newer models, and others (thalidomide) have risen from the dead to find new life in novel therapeutic fields.

So what do I chose?

The devil I know or the devil I don't know?

The honest answer is that I never really know anything fully.

Like the gift of any photograph, I get the truth, but it is always incomplete and always has a built in point of view.

The best I can do is to calmly contemplated the options, purposefully act, and stay aware.

And have my trusty team in place for when I can't.