ASH 2019 Day 1 – CAR T-Cells Session

DAY 1 – Morning Session 1

We kick off this year’s American Society of Hematology (ASH) meeting covering two presentations that discuss the very hot topic of chimeric antigen receptor (CAR) T-cells. In CAR T-cell therapy, regular/normal T cells are “supercharged”. The process of “supercharging” the T cells involves extracting them from a myeloma patient, making genetic changes to them in a lab (turning them into more effective myeloma detectors and killers!), and then re-infusing them into the patient. Once back inside the patient, the improved T cells (that is, CAR T cells) resume their search-and-destroy mission against myeloma cells.

In this morning’s session we heard about a new kind of CAR T-cell therapy, one that is engineered a bit differently than other CAR T-cell therapies in development for myeloma.  And, we learned about another CAR T-cell therapy that is engineered to seek out myeloma cells that have a marker called B-cell maturation antigen (BCMA) on its surface. BCMA-targeted CAR T cells are the most common CAR T-cells that are in clinical trials.

The team of clinicians at the University of Pennsylvania (where CAR T-cell therapy was born!)—led by Dr. Edward Stadtmauer—used a different target than BCMA to supercharge T cells—called NY-ESO-1. Additionally, they engineered the T cells even further to improve their ability to kill myeloma cells and stay in a patient’s body longer. They tested these new cells (called NYCE T cells) in patients for the first time (ABSTRACT 49 https://ash.confex.com/ash/2019/webprogram/Paper122374.html). Only 2 patients with myeloma who had previously received 7-8 other therapies (including stem cell transplants and many common myeloma drugs) received treatment with NYCE T cells. Both patients tolerated treatment well without neurotoxicity or cytokine release syndrome (CRS). One patient progressed on treatment and the other is still too early in treatment to evaluate for response. The investigators will continue to refine their engineering process for this therapy. Stay tuned.

The latest CAR T-cell therapy discussed this morning—called C-CAR088—is a BCMA seeker (ABSTRACT 50 https://ash.confex.com/ash/2019/webprogram/Paper125372.html).  Researchers out of Shanghai, China designed C-CAR088 to tightly latch on to BCMA on myeloma cells and to potentially be safer than other CAR T-cells and not cause severe side effects.  Researchers presented their results of a phase 1 study with C-CAR088 in only 3 patients with relapsed/refractory myeloma. These patients had previously received 7 lines of therapy and failed immunomodulatory drugs (like Revlimid) and proteasome inhibitors (like Velcade)—so these were considered very heavily pretreated patients. Within 2 weeks after C-CAR088 was given, all 3 patients showed clinical improvement (2 patients achieved a very good partial response and the other achieved a partial response). The researchers reported that treatment was tolerated by patients and caused only mild, but manageable, cytokine release syndrome (CRS). Ultimately, C-CAR088 compares favorably to many other anti-BCMA CAR T-cell therapies under investigation and it will continue to be studied in clinical trials—so be on the lookout for new updates in the coming years.