In November, 2014, I attended a meeting in Thessaloniki, Greece organized by the European School of Hematology (ESH), ESH 2014: International Conference on New Concepts in B Cell Malignancies: From molecular pathogenesis to personalized treatment. This video interview discussing predictive and prognostic markers in chronic lymphocytic leukemia (CLL) is with Prof. Dr. med. Stephan Stilgenbauer of the University of Ulm.
TAKE AWAY POINTS
- Prognostic markers help predict the likely outcome of cancer for a group, but less so for any given individual.
- Predictive markers help predict the likelihood of benefiting from a particular therapy.
- Only checking for deletion 17p will miss many cases where p53 is not working.
- The clinical implications of these markers are changing with new therapies.
During my interview with Prof. Stilgenbauer, we reviewed the topic of predictive and prognostic markers in CLL. Here is a link to an earlier post on another aspect of this subject with Dr. Bill Wierda from MD Anderson. Dr. Jeff Sharman discusses some of the same material in this helpful post from iwCLL 2013.
The first message that I gathered from Prof. Stilgenbauer is that the significance of all these factors must be reassessed in this era of novel therapies and that process has only just begun. How they may have predicted and prognosticated about treatment with FCR is not always going to match up to their relevance for therapy with ibrutinib or idelalisib.
This should be an active area or reassessment and research. One possible example seems to be that patients with 17p deletion respond differently when treated upfront with ibrutinib versus when treated following relapse. More predictive and prognostic factors will emerge if we look.
My next take way: It is no longer sufficient to test only for the deletion of the short (p for petite) arm of the 17th chromosome (17p deletion), but we also must ask our hematologists to check the function of the TP53 gene. TP53 has been called the guardian of the genome. When it is functioning well, it protects our genetic information from being miscopied and thus spawning a malignant offspring. When it is missing or dysfunctional, cancers are both meaner and harder to kill. Here is a nice overview on TP53 from the National Institutes of Health. Dr. Stilgenbauer discusses the relation between TP53 and 17p deletion.
Finally, with the advent of deeper probing of our cancer’s genetic makeup with next generation sequencing, we touch briefly on some of the new prognostic factors found in CLL. These include mutations in NOTCH1 (a signaling pathway between adjacent cells) and SF3B1 (a surprise finding, a important in gene splicing). Here’s the original article from the NEJM that goes into much greater detail.
Here is Dr. Stilgenbauer.
Brian Koffman 12/15/2014