Ten years in leukemia remission thanks to CAR-T cell treatment

A decade ago Bill Ludwig and Doug Olson were seriously ill, suffering from a type of leukemia that no longer responded to treatment. Both were the first to undergo what was then a new cell therapy, CAR-T, which has kept them in remission for ten years.

A study published today by Nature collects details on the greater persistence of CAR-T therapy recorded to date against chronic lymphocytic leukemia (CLL) and shows that these cells remain detectable ten years after treatment with sustained remission.

Chimeric antigen receptor (CAR) T-cell therapy is a living drug made for each patient from their own cells.

It involves collecting T lymphocytes, which are part of the immune system, modifying them through genetic engineering in the laboratory and re-administering them to the patient so that they attack cancer more effectively.

When they were the first to participate in a clinical trial at the University of Pennsylvania (USA) ten years ago, Olson had been ill since 1996 and Ludwig since 2000, their condition was very complicated and they were left with no options for survival.

However, the novel treatment would eradicate his end-stage leukemia the same year it was applied, ushering in a new era of highly personalized medicine.

“This long-term remission is remarkable, and to see patients live cancer-free is a testament to the tremendous potency of this ‘living drug’ that works effectively against cancer cells,” said Joseph Melenhorst of the University of Pennsylvania and the study’s first author.

To this day, Olson, a former scientist, is still in good health and even runs half marathons, however Ludwig passed away in early 2021 due to complications from covid-19.

Chronic lymphocytic leukemia (CLL) is the first cancer in which CAR-T cells were studied and used at the aforementioned university and the most common type of leukemia in adults.

Over the years, treatment has improved, but it is an incurable disease with standard approaches, and over time, patients can become resistant to most therapies.

The researchers looked at the evolution of CAR-T cells over time, with the appearance of a population of highly activated CD4+ lymphocytes that became dominant in both patients.

The data suggest two distinct phases of responses to CAR-T cell therapy in these patients. The initial dominated by so-called killer T cells and a long-term remission controlled by CD4+ T cells.

In subsequent years, CD4+ cells continued to demonstrate characteristics of tumor cell destruction and continued proliferation, which is “a hallmark of CAR-T cell efficacy against cancer: their strong ability to survive and thrive within the body.” said the University of Pennsylvania.

This therapy has been “extremely effective for specific leukemias and lymphomas and we hope to continue our efforts in these cancers while studying its impact on solid tumors with research in this area to see further development in the coming years,” highlighted another of the authors of the investigation, David Porter.

The university has begun testing next-generation T cells in more blood cancers, including lymphomas, and against challenging solid tumor cancers.