Take Away Points:
- As the CAR-T technology improves, new targets for many cancers are being researched and identified.
- When the re-infused T cells recognize our cancer, they activate and release large amount of cytokines (small proteins that direct communication and behavior between cells) resulting in a life threatening cytokine release syndrome (CRS) or cytokine “storm.”
- Blocking one particular cytokine called interleukin-6 with the drug, tocilizumab, often times calms the cytokine “storm”, but the timing of the intervention may be critical.
- CAR-T therapy, though generating considerable optimism, is still in its infancy.
Hematology in general and CLL specifically are full of jargon and acronyms that can be both overwhelming and daunting. With time and experience, you’ll become familiar with the terminology and acronyms. We will try to explain each medical term the first time it appears in an article, but we will use the true terminology so that you gain comfort and familiarity with the medical terms that you will see in your lab reports and in medical articles. We have provided a glossary and a list of abbreviations and acronyms for your reference.
CAR-T Therapy: The Downside
This is a follow-up to part one on CAR-T that should be read and viewed first.
Here Dr. David Porter from the University of Pennsylvania talks about the worrisome side effects of CAR-T cell therapy in the weeks following the re-infusion of our T cells when the new T cells wake up and in his words ”get angry.”
He discusses what is known and not known about cytokine release syndrome. Using the drug, tocilizumab, already approved to treat inflammation associated with Rheumatoid Arthritis, can often abrogate the severe reaction. When exactly to intervene is not known, as this dangerous inflammatory reaction to the CLL cells may also be beneficial in killing the cancer, provided we can safely weather the storm. This intervention issue also arises with the tumor flare sometimes seen with lenalidomide where fully blocking the flare may diminish the therapeutic benefit of the drug.
This tightrope walk is the art of medicine and Dr. Porter reminds us at the end of the interview that CAR-T therapy is still reserved for those who have run out of other options.
Here’s my opinion —
The role of CAR-T therapy in CLL is uncertain and much more research is needed before CAR-T is a routine option in CLL. It would help to identify more tumor specific targets such as ROR1 (Receptor tyrosine kinase-like orphan receptor 1, a surface marker found on CLL cells but not normal B cells). A suicide switch in the chimeric T cells would also be beneficial. We need to better understand why some of us respond dramatically but many of us do not respond at all. A more standard approach to address the difficulties of therapy must be established. All that and more must be in place before CAR-T is ready for use outside clinical trials.
That said, I am sure that will all happen, and probably much sooner than we might imagine.
Brian Koffman March 1, 2015 with help from SA