ASH 2013: Dr. Adrian Wiestner Discusses Prognostic and Predictive Factors, the Nuances of 17p deletion and Residual Disease
In the second part of the interview from ASH 2013 in New Orleans, Dr. Adrian Wiestner from the NIH gives us some very carefully considered reflections on the news from the cutting edge changes in our understanding of CLL.
I first asked him to revisit the important issue of predictive versus prognostic factors that I first discussed at iwCLL with Dr. Sharman.
His review of 17p deletion, particularly for those lucky few who are mutated with 17p is very hopeful and nuanced. Listen carefully.
Dr. Wiestner suggested a cut off of 25% to define high risk 17p deletion. The reality is that it depends. While Dr. Tam's research in Blood on de novo 17p del (from the time of diagnosis and not first appearing after treatment) find prognostic significance only when more than 25% of the nuclei are missing the small arm of one of the 17 chromosome, others suggests a lower cut of 20%, some 10%, and some as low as 5% in looking at all cases, de novo and acquired, of 17p deletion. Like many subjects in CLL, consensus is lacking.
My simple take is the less 17p, the better. None is the best.
And we all know that the less disease, the better. Dr. Wiestner points out the obvious but we we need to hear it: You have to get to MRD (minimal residual disease) negativity to get to cure. What does this mean for the new drugs that rarely seem to get to CR, let alone MRD negative? Dr. Wiestner shares some thoughts.
Keep in mind also that 17p is a bad player in that not only does it not allow apoptosis (cell suicide) in response to most chemotherapy and thus rendering common CLL drugs such as fludarabine and cytoxan most ineffective, it also allows the cancer cells to mutate (genomic instability) with no controls on a clone gone bad. Add this clonal devolution to a significant population of residual cancer cells and we begin to understand why initial responses to the new agents such as ibrutinib and idelalsib are excellent, but sadly late relapses are more likely in those of us with a deleted 17p.
This seems to me to be a strong call for dual therapy for the 17p population, but whether that is the answer will only be answered with clinical trials.
Let's listen to Dr Wiestner.
We are so lucky to have a team of doctors working to solve our issues.
More interviews soon.