At the 2014 American Society of Hematology annual meeting in San Francisco, Professor Peter Hillmen from the University of Leeds explains the important role played by surrogate markers in predicting relapse and suggesting logical combinations with targeted therapies.
Take Away Points:
- Biological markers may inform who will do best with any particular therapy and which combinations make the most sense.
- MRD (minimal residual disease) negativity is probably still an important predictor of long-term disease control even with targeted therapies.
- Molecular changes precede clinical changes and suggest who might benefit from adding a second agent.
In the second part of my interview with Professor Hillmen, he explains the important role played by surrogate markers. Dr. Hillmen is of the school that MRD negativity remains a critical indicator of how well we will do long-term even in the era of targeted therapies. I tend to agree. I would however question his reflection that the speed to reach MRD negative status is also important.
That maxim does hold true for chemo-immunotherapy. We know that mutated patients can take longer than unmutated patients to resolve the early lymphocytosis (raised lymphocyte counts) often seen with the new signal blockers such as ibrutinib and idelalisib. This early lymphocytosis occurs as cancer cells leave the bone marrow and the shrinking lymph nodes for the less protective environs of the blood stream. Those same ‘slow to get back to normal’ mutated patients may do better in the long run than their unmutated friends. Slow and steady may be better than quick and mercurial. See this article in Blood out of Ohio State University for more details. I quote from the paper by Dr. Jennifer Woyach: “Most interesting is the finding that patients with persistent lymphocytosis over 1 year have a similar PFS [progression free survival], with a trend toward a superior outcome compared with those who achieve an objective response within this time frame.”
We are still discovering the similarities and differences of these new targeted therapies compared to standard chemo-immunotherapy. That’s why Professor Hillmen’s research is so important.
Please give a listen.
Brian Koffman 5/9/15