Novartis team tracks remissions of 4-plus years in a pioneering CAR-T study

Dr. Carl June

Five years after the University of Pennsylvania began recruiting a small group of 14 patients with hard-to-treat chronic lymphocytic leukemia, researchers are still tracking three of them who are still alive with no signs of their cancer returning after being treated with a first-generation CAR-T therapy. 

The study offers a glimpse into the promise of a durable response for reengineered T cells--in this case taking the T cells out of patients and then adding a chimeric antigen receptor for a treatment called CTL019, which is owned by Novartis ($NVS)--while outlining the challenges involved in keeping patients safe from a severe and common reaction and devising new approaches to overcome some of the personalized treatment's limitations as the first of these drugs move closer to a possible marketing approval. The results were published in Science Translational Medicine.

Out of the 14, four experienced complete remissions, meaning their cancer was no longer detectable. One of those four later died of other causes. Four patients had partial responses, with two of them dying after 10 months and 27 months of therapy. One of the partial-response patients died from a pulmonary embolism, and the other was switched to a different therapy after 13 months and died after three years.

Six of the patients did not respond to the therapy. And of the three patients still alive, two were treated more than four years ago, making them the longest running remissions in the CAR-T field.

The key takeaway:

"Importantly, our tests of patients who experienced complete remissions showed that the modified cells remain in patients' bodies for years after their infusions, with no sign of cancerous or normal B cells," said the study's senior author, Dr. Carl June, one of the pioneers in immunotherapy, which is emerging as a multibillion-dollar market. "This suggests that at least some of the CTL019 cells retain their ability to hunt for cancerous cells for long periods of time."

All of the patients who responded to the therapy experienced a potentially life-threatening case of cytokine release syndrome, sometimes called a cytokine storm, with the drug triggering high fevers and in several cases difficulty with breathing and low blood pressure. Doctors responded with the antibody drug tocilizumab and steroids, and all of the patients survived.

In a small study like this, investigators can learn as much from failure as they can from success. Testing the 6 patients who did not respond, the scientists said that their customized T cell populations did not expand as aggressively as in the patients who were first flattened by a cytokine storm in their first response to the solo treatment.

The Novartis/Penn team as well as rivals Juno ($JUNO) and Kite ($KITE) and a whole pack of companies jumping into the game have been studying new technology that can be used to amp up the T-cell attack on cancer cells. A whole host are also tackling the challenge of moving past B cells to solid tumors and off-the-shelf therapies, which represent a big challenge--and a much bigger market.

- here's the release
- get the research abstract