iwCLL 2017: Prof. Hillmen on MRD Negativity in CLL (chronic lymphocytic leukemia)

At iwCLL 2017, in Manhattan, I interviewed Professor Peter Hillmen from Leeds who heads the innovative chronic lymphocytic leukemia (CLL) research efforts in the UK.

In past interviews at ASH 2014, we have discussed TAP or the Trials Acceleration Programme in a three-part interview. All three parts can be accessed here. Reviewing that interview will help put this conversation in context and give a sense of how fast we are progressing.

Because he is so interested in looking for helpful biomarkers to speed up research and to improve patient outcomes as quickly as possible, I was particularly excited to hear Prof. Hillmen’s take on MRD or minimal residual disease in CLL.

Being MRD negative means there is no detectable cancer. That does not mean there is no cancer. It just means that the amount of cancer that is possibly hiding in the blood or bone marrow is below the threshold of the latest technology to find it. Today that means that less than one cell out of 10,000 is a CLL cell.

Achieving MRD negativity in CLL has been well proven to be a good thing when using tradition chemo-immunotherapy (CIT) such as FCR. It is highly predictive of longer progression-free survival (PFS) as explained here and in several other similar articles.

The question today is: Does MRD matter as much with the use of novel therapies?

Take Away Points:

• MRD is minimal residual disease or perhaps better called measurable residual disease.
• New non-chemo therapies such as venetoclax and other combinations are achieving MRD negative status which allows us to see if we can:
  • Stop therapy and have patients continue to do well long-term.
  • Cure patients, especially frontline patients with the right combinations of non-chemotherapies. (See the Cake of Cure for Dr. Byrd’s upbeat take on this topic.)
• Only through more clinical trials will we answer these questions.

Since our interview, JAMA Oncology published this article on the role of MRD in novel therapies where the authors said:

“Given the heterogeneity of CLL biology and therapies, this validation must be regimen specific.“

What this means is that even though we know MRD is an important prognostic marker and perhaps a surrogate for PFS with CIT, we don’t yet know that for novel therapies. It is important not to generalize in CLL research.

Listen to the audio interview with Professor Hillmen below or read the transcript here.

CHEERS!

Brian Koffman, MD 8/8/17