At ASH 2018, I interviewed Dr. Siddiqi of City of Hope concerning the CAR-T trial with JCAR-17 or Liso-cel that is directed against CD19, a marker on the surface of CLL cells.
CAR-T cells are genetically engineered T lymphocytes that have been grown outside of the body and trained to attack CLL cells, then reinfused into the patient. They are a living drug. For more on the basics of CAR-T and its risks, please see https://cllsociety.org/car-t-and-other-cellular-therapies/.
You might want to start with the CART comic book.
Dr. Siddiqi presented the early data on the first 16 patients. These were a very difficult group to treat with high risk features and advanced stage disease who had failed prior therapies including ibrutinib.
- CAR-T cells could be manufactured for 100% of the patients despite prior treatments that could have damaged the T cells ability to grow.
- 75% of patients had cytokine release syndrome (CRS) but only had 1 had grade 3 CRS who needed to be cared for in the ICU.
- The most common CRS symptoms were fever and chills.
- All CRS was reversible.
- 37% had neuro events and 3 of the 16 had significant confusion or other neurological symptoms.
- All neuro events were reversible.
- Only 3 patients had tumor lysis syndrome (TLS) that was easily managed.
- 81% response rate, 43% had a complete response, mostly very quickly.
- Responses got better from day 30 to day 90 or 180 with no further treatment as the CAR-T cells persisted and continued to wipe out any residual CLL.
- At day 30, 71% were U-MRD (undetectable minimal residual disease) in the peripheral blood and 7 of 8 were U-MRD in the bone marrow. What that meant is that no cancer was detected down to 1 cell in 10,000.
- All patients who were U-MRD had not progressed at the time of the interview, though the follow-up was short.
- Ibrutinib improves T cell function and will be used in future trials to see if we can achieve even deeper responses.
- Trials are ongoing.
In my 15-minute interview we stop to explain all the terms in the bullets above in more detail.
Please enjoy as Dr. Siddiqi walks us through her promising early data in an experimental gene therapy for CLL that is very similar to the treatment that I received and has provided me with a deep and durable remission.
Here is the link to the actual ASH abstract:
This is both good stuff and tough stuff, but overall the future looks bright.