CAR-T CELLS NOT READY FOR PRIME TIME

Extraordinary results" and "unprecedented responses" with chimeric antigen-receptor (CAR) T-cells in hematological malignancies have made headlines in media outlets across the world after researchers reviewed new results at the American Association for the Advancement for Science (AAAS) annual meeting in Washington, DC, held from February 11 to 15.

The results are not new, and this excitement over CAR T-cells has bubbling now for 2 years. But a recent report from a major cancer organization cast some doubt over whether this approach would ever become widely used.

"It is not yet clear if CAR T-cell therapy will have broader use in the future," comment the authors of the recent Clinical Cancer Advances report from the American Society of Clinical Oncology. While they highlighted CAR T-cell therapy as a clinical advance because of the promising data in patients with hematological malignancies, the authors point out that the results so far have come from studies that "were small and limited to patients with hard-to-treat cancers." Also, they note that this approach can cause considerable toxicities and, as a result, so far it is currently administered only in specialized clinical centers.

The CAR T-cell approach, which involves taking T-cells from patients, engineering them, and then re-infusing them back into the patient, has produced dramatic results in clinical trials in leukemia and lymphoma patients, as previously reported by Medscape Medical News.

At the AAAS meeting, Stanley Riddell, MD, from the Fred Hutchinson Cancer Research Center in Seattle, which is now working with Juno Therapeutics, reviewed results from clinical trials so far. This approach has achieved "sustained regression" in many previously relapsing and treatment-resistant cases of B-cell malignancies — acute lymphoblastic leukemia, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia — he said in a press statement.

Dr Riddell highlighted one study in which 94% of participants with acute lymphoblastic leukemia saw symptoms vanish completely, according to a report in the Guardian. Patients with other blood cancers had response rates greater than 80%, and more than half experienced complete remission, he said.

"This is unprecedented in medicine, to be honest, to get response rates in this range in these very advanced patients," Dr Riddell said.

Nothing like this has been seen before, said Chiara Bonini, MD, a hematologist at San Raffaele University in Milan, who also presented data at the meeting. "This is really a revolution," she said.

At the meeting, Dr Bonini reported a trial in 10 patients, in whom researchers had tracked the presence of "memory" T-cells for 2 to 14 years after they had been introduced. She described the T-cells as a "living drug...with potential to persist in our body for our whole lives."

She also said the modified memory T-cells could eventually provide a long-term defense against cancer, using cells that "remember it from 10 years earlier, and kill it so quickly you don't even know you're infected," according to the Guardian report.

Companies Now Involved

The CAR T-cell approach has been making headlines for the last 2 years, and while at first these results were from small trials conducted at research institutes, a number of companies have now become involved and are all working to bring this technology to the market.

In addition to Juno Therapeutics, which is working with the Seattle Children's Research Institute and the Memorial Sloan Kettering Cancer Center in New York City, as well as the Fred Hutchinson center, there is also Novartis working with the Children's Hospital of Philadelphia and the University of Pennsylvania, and Kite Pharmaceuticals (which has teamed up with Amgen) working with the National Cancer Institute. Also in this field are Pfizer (working with Cellectis SA, France) and Celgene (working in collaboration with Bluebird Bio Inc. and Baylor College of Medicine).

The challenge facing these companies is to get an experimental approach, which is custom made for each patient, to a state where it can be marketed as a product.

A market report published in 2015 commented that CAR T-cell therapy "looks like it's becoming little short of a revolution in the treatment of some cancer types," but it also warned that "numerous risks are being lost in the hype." The report notes that that very few patients overall have been treated through CAR T-cell clinical trials, and there have been severe adverse events that have led to patient deaths. It also cautions that with so many institutions and companies now involved in this field, there may yet be extensive litigation over intellectual property.

The comments made at the AAAS meeting were picked up by numerous other media outlets, such as the Daily Mail and BBC News in the United Kingdom, all of which presented the results as a "breakthrough" in the treatment of cancer, although most noted that this research pertained only to blood cancers.