COMMENTARY

CAR T-Cell Therapies: Broader Indications, Bigger Problems?

Leonard B. Saltz, MD

Disclosures

June 29, 2018

Hello. I'm Leonard Saltz, professor of medicine at Weill Cornell Medical College, and executive director for clinical value and sustainability and head of the Colorectal Oncology Section at Memorial Sloan Kettering Cancer Center, both in New York City.

Chimeric antigen receptor (CAR) T-cell therapies are one of the more exciting developments in our armamentarium for treating patients with cancer.[1,2,3,4,5,6] One of the most exciting changes in the past year is having CAR T-cell therapy commercially available as nonresearch tools for patients with selected malignancies.[6,7,8] One downside, of course, has been the astronomical cost involved in patients receiving these therapies.[7,8] The individual drugs themselves cost between $400,000 and $500,000, and the amount of additional care that patients require may equal that amount or more in some cases.[7,8] The question is, what are we getting for this exciting new therapy and to what degree is this going to be a problem, as we expand this technology to broader indications?

Currently available CAR T cells target CD19, limiting their utility to certain types of leukemias and lymphomas.[9,10] This is a relatively small population compared with the population of patients with solid tumors, but there are over 150 clinical trials that are seeking to develop CAR T-cell technology for patients with solid-tumor malignancies.[9,10,11] Thus far, results have been somewhat less encouraging, in terms of both frequency and durability of responses, but they're going to demonstrate some clinical activity.[11,12]

As a society, we are going to have to wrestle with several questions. What are [these therapies] delivering, and are they worth it?[12] What is it costing us, and can we afford it?[12,13] These open questions that don't have specific answers, but they're going to need to be addressed.

It's also important to keep a certain amount of balanced perspective on what CAR T-cell technology has provided so far. For some patients, they deliver long-term disease control and possibly even a cure.[1,2,3,4,5,6] For many other patients, we're seeing [tumors develop] escape mechanisms, with CD19-negative leukemias emerging, or other mechanisms such that CAR T-cell therapy is far from curative for many of the patients.[14,15]

I have already heard discussions from my leukemia colleagues about incorporating CAR T-cell [therapy] into algorithms, with plans to use bone marrow transplant either before or after.[16] Again, these highly involved, highly toxic, and highly expensive therapies are going to start to really add up in terms of the cost of individual patient care, and at some point, we're going to reach a breaking point.[1,2,3,4,5,6,7,8] This is not to belittle the importance of the science and the importance of the clinical benefit that some patients are achieving, but to deny the financial realities and financial toxicities involved is not going to be helpful in terms of figuring out how we can bring this technology forward to patients who really need it.[16]

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