iwCLL 2013: Dr. Jeff Sharman Discusses the Practicalities of the New Prognostic Factors

In this short but rather technical discussion of the new diagnostic tests that is a follow-up to part one of my interview from iwCLL 2013 in Cologne, Germany, Dr. Sharman shares what he actually tests for in a patient who is considering therapy.

I started by challenging him that we have heard of these novel disease markers such as BIRC3, Notch 1 and SF3B1, but they are not discussed much outside of academic research, and even then, they are not tested for in most trials

Most of these new prognostic markers have just not yet made it from the research studies into the hematologist's office.

One important point that I want to linger on for a moment is the difference between a prognostic and a predictive marker.

Though the terms are often used rather loosely, and many markers are clearly both, there is a difference.

A predictive marker tells us patients how likely we are to respond to a particular therapy. A 17p or BIR3 or CYP2B6*6 warns us that our chance of a response to FC is markedly diminished.

Mutation status prognosticates how likely we are to need therapy and die too soon from our disease. Remember that all prognostic markers are prognostic for groups, not for individuals

While there is frequent overlap, it is a helpful distinction to keep in mind when considering our  workup in advance of therapy. Obviously a marker that predicts that we won't do well with traditional chemo-immunotherapy carries with a bad prognosis if that is the only therapy our docs could offer.

But as you have heard over and over again, that dangerous bottleneck is rapidly expanding with the new treatments coming into use. Accordingly, the distinction becomes increasingly important and predictive tests may soon help guide choice of our therapy.

Here is Dr. Sharman:



One more sad note: I just found out that another CLL warrior lost the fight. George Martinez, whom I met and connected with in Columbus, Ohio, a fellow charter member of Team I (ibrutinib) who like me, flew to Ohio from his home in SoCal to join Byrdland, came to that drug after being badly beaten up by his CLL, its treatment, and multiple horrific infections.

I will miss his kind, funny, warm and generous ways.

We need to be looking at more than kicking the cancer down the road. We need to looking at reconstituting our immunity and preserving our marrow.

I hate this disease and want to see it vanquished!

Rest in peace, George.

iwCLL 2013: Day One

So far iwCLL 2013 has been a very cutting edge and bench science driven conference. Great stuff, but not easy stuff to digest.

Tomorrow that changes with more "clinical" presentations.

I need to sleep and not blog, but expect video interviews when I get home from three of the speakers today: George Calin on micro-RNA, Juan Castro on the micro-environment, and Jan Burger on a review of all the mid morning presentations.

This is important stuff we patients need to understand and the doctors that I interviewed do a great job of making it accessible. This is the basic science that molds the future of therapy that they are discussing.

Spent hours reviewing the many excellent poster presentations.

One tidbit: Notch1 and 11q del may be mutually exclusive. Who knew?

My brain is exploding. So much new information.

I will try to hold your hand as I share over the next several weeks all that I have discovered here in Cologne on day one.

Met many old friends and made some new ones. Working hard on some patient advocacy plans with some of the people here. Stay tuned.

Tomorrow looks to be just as busy or busier with at least three interviews lined up, but everything changes at the last minute.

But my son and I will make the time to get out of the conference center and see the famous cathedral before we leave. That is a must. It is only a short walk (in the rain) from our hotel.

But first I must sleep.

ASCO 2013: Dr. Wierda on Prognostic Factors in CLL (Chronic Lymphocytic Leukemia)

The whole arena of prognostic factors in CLL is constantly evolving, but a few principles have remained constant over the years.

1: Most, if not nearly all the data is retrospective.

2: Dr. Wierda and many others are refining algorithms that will weight the many variables to better predict our future including such helpful information as the expected time to first treatment or our chances of a durable remission or ultimately our chances to live long and prosper.

3: The markers predict for groups, not individuals, but that doesn't mean we should be therapeutic nihilist and ignore what our FISH tests tell us about what options improve our odds.

4: Bad prognostics are not in themselves an indication for treatment (outside a clinical trial).

5: Good prognostics doesn't always mean that our CLL will be a non-event.

6: New prognostic factors are being discovered all the time, but few will be of much clinical import.

Here is the second part of my interview with Dr. Wierda from ASCO 2013.

I will let him fill in the details on all these topics and other aspects of this moving target.

Again my thanks to  my friends at Patient Power for sharing the work and supporting the effort to get the important news about CLL from ASCO out and available to all those of us who need it to inform our choices about how we handle our disease. Check in on their website on a regular basis as Andrew Schorr is frequently update his informative site.



In fairness, I must add that other researchers have published data supporting a possible relationship between Notch1 and Richter's Transformation (or Syndrome),

I quote from a letter in the British Journal of Haematology, 2012, 158, 415–429


"NOTCH1 mutations were associated with a ~5·8-fold increase in the crude hazard of transformation into a clonally related RS (Richter's Syndrome) "

This is from an editorial from haematologica | 2012; 97(3)

"In fact, the first studies reported a high frequency of NOTCH1 mutations in .... disease progression towards transformation into Richter’s syndrome."

Now this is not the same level of evidence as in a full article, and as such might not pass mustard for Dr. Wierda and others as proof positive of the correlation, but it convinced me that it is worthy of further study.

There is just too much data out there for anyone of us to be aware of it all.

And that's OK.