We have increasingly recognized that it is not enough to only target, but we also need to target where it lives.
Dr. Yucai Wang is a hematology fellow at Mayo, MN who researched the micro-environment in both CLL and Richter’s transformation.
We discussed his findings at ASH (American Society of Hematology) Annual Meeting 2018 in San Diego.
- The study looked at samples of patients treated with pembrolizumab (anti-PD-1 immunotherapy) for both Richter’s Transformation (RT) and aggressive chronic lymphocytic leukemia.
- While some patients with RT, none with CLL responded.
- It turns out that the part of the reason for this might be explained by differences in the micro-environment, the cells surrounding the cancer, that support RT versus CLL.
- PD-1 is more expressed in the RT micro-environment.
- More T cells (the cellular soldiers to fight cancer) were seen in RT.
- The T cell population was more diverse than the weak immune response seen in T cells fighting CLL.
- This research suggests that manipulating the micro-environment might help improve responses in CLL.
We have known for a while that part of the efficacy of drugs such as ibrutinib, idelalsib, and duvelisib is how they block the signals that keep the CLL cells nested in their micro-environment in the bone marrow and the node. When the CLL cells are out in the blood they are easier to kill. Dr. Wang furthers this understanding by looking at what is going on in the micro-environment that helps the CLL cells.
Using combinations that effect the micro-environment and the cancer itself might be important going forward.
Here is my interview with Dr. Wang.
Here is a background abstract on PD-1 expression.