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ASH 2018: Dr. Neil Kay on how Stromal Cells Keep CLL (chronic lymphocytic leukemia) Cells Alive in the Bone Marrow and How we Can Intervene

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At ASH 2018 in San Diego, CA, I interviewed Dr. Neil Kay out of Mayo Clinic, Rochester, MN, an innovative chronic lymphocytic leukemia researcher who besides caring for CLL patients and conducting clinical trials, is doing important “bench” science where we are fortunate to find insights that can transform how we best knock out the CLL cells.

Dr. Kay’s research presented at ASH 2018 was on the supportive stromal cells in the bone marrow, formally known as mesenchymal stromal cells (MSCs).

Takeaways:

  • Stromal cells are part of a network of cells in the bone marrow that help keep CLL cells from dying.
  • Kay’s lab has built a model of MSCs supporting CLL cells for experimentation.
  • They discovered that the marrow stromal cell mediated increased expression in two enzymes, β-catenin and Axl in CLL B-cells is associated with leukemic cell survival and drug resistance.
  • The experimental drug, TP-0903 blocks Axl and reduces CLL cells’ survival and their ability to resist chemotherapy.

Conclusions:

It is easy to forget that ibrutinib was only developed as the amazing breakthrough for chronic lymphocytic leukemia when the importance of the B-cell receptor (BCR) to CLL cells survival was recognized, in other words, when that biology was cracked.

Dr. Kay and his team is trying to do the same kind of thing with this research and it has quickly gone from bench to bedside in a clinical trial using TP-0903 alone or in combination with ibrutinib: Phase 1/2 Study of TP-0903 (an Inhibitor of AXL Kinase) in Patients With Previously Treated CLL.

It is an intriguing direction, attacking the soil, not just the seed of cancer. For more of the importance of cancer micro-environment, see my interview with Dr. Wang, also from Mayo.

While the science may be less accessible than when we talk about clinical trial results, there would be no new drugs for clinical trials without this basic laboratory research.

Here is my ASH 2018 interview with Dr. Kay.

Here is the actual abstract.