JAMA Commentary Urges Realistic View of New CAR T-Cell Cancer Therapy

While the FDA’s approval of the immunotherapy tisagenlecleucel represents a landmark in the oncology field, the treatment is far from being a cure and should be viewed in context of its $475,000 price tag, a group of oncologists wrote in a commentary published in JAMA.

The 3 oncologists from Memorial Sloan Kettering Cancer Center acknowledged the “impressive science” behind the therapy marketed as Kymriah, which involves genetically modifying each patient’s chimeric antigen receptor (CAR) T cells to target and kill tumor cells. Indicated for pediatric and young adult acute lymphoblastic leukemia, Kymriah is the first CAR T-cell therapy approved by the FDA and “heralds a new era of treatment,” they wrote.

However, the therapy does carry the risk of significant side effects, since the modified cells can also damage healthy cells and tissues, and it is known to cause cytokine release syndrome in some patients, which can be dangerous or even fatal. The technique needed to extract, engineer, and re-inject the patient’s T cells is challenging, so the authors emphasized that it will only be available at a handful of capable institutions.

Another factor contributing to their hesitation is the price of Kymriah; its manufacturer, Novartis, has set a price of $475,000 per course. The authors noted that it is difficult to compare the cost effectiveness of this therapy to other cancer treatments because it is both more efficacious but also substantially costlier than the other treatments, which already have high prices.

Furthermore, the authors point out that the final cost of treatment with Kymriah will rise higher than $475,000 after accounting for toxicity management efforts, treatment of events like cytokine release syndrome, and necessary preinfusion and postinfusion procedures. Expanding the therapy’s indication to other cancers and populations would further increase the cost burden on patients and the healthcare system, even though “the health benefits could be substantial.”

Published less than a week after a group of US Representatives wrote a letter to CMS asking for more information on the outcomes-based payment agreement developed with Novartis for Kymriah, the JAMA commentary also raised questions about the specifics of this agreement. The authors proposed some alternate endpoints that may be better surrogates for clinical benefit, but acknowledged that “arguably a more important issue that choosing the right end point is starting at the right price in the first place.”

Finally, the commentary authors wrote that another danger to the appropriate use of Kymriah and other CAR T-cell therapies is the popular hype surrounding the treatment. They advised clinicians to clearly explain the potential benefits and risks of these approaches to patients, including a thorough description of the potential side effects.

Above all, the authors warned clinicians, scientists, and members of the media to avoid using the word “cure” in discussions about CAR T-cell therapies, despite the widespread excitement surrounding them.

“The reason is that the term cure will connote to some patients that a single infusion of this scientifically mystifying, genetically driven therapy will first vanquish their disease and then reset their life expectancy to normal,” they wrote. “Perhaps one day data will support such a hope; as of yet the available data are insufficient to claim much more than CAR-T treatments have large promise at an enormous price.”