In August 2017, the U.S. Food and Drug Administration (FDA) made available to the United States the first-ever gene therapy for cancer and other life-threatening diseases called chimeric antigen receptor T-cell, simply known as CAR T-cell or CAR-T.¹

This historic approval was a godsend to children like 12-year-old Emily Whitehead who, suffering from leukemia at that time, underwent this novel form of immunotherapy that achieved effective results.² Accordingly, the two drugs released were Kymriah (tisagenlecleucel) for acute lymphoblastic leukemia (ALL) for children and adults, and Yescarta (axicabtagene ciloleucel) for patients with different types of large B-cell non-Hodgkin lymphomas (NHLs).³

Regarding the subject, an oncologist at Penn Medicine, Stephen Schuster, said to an online source, “We’re saving patients who three or four years ago we were at our wit’s end trying to keep alive.”⁴

Although these medications offer a beacon of hope to those affected by previously incurable conditions, the CAR T-cell drugs have been indicated to be one of the most expensive for patients and the healthcare system as a whole.⁵ In addition, the method has a stringent approval process, that is to say, the drugs cannot be administrated to all cancer patients. Certain studies have also made known the inclination of this treatment towards serious side effects in users.²

However, despite these limitations and owing to the promising (often considered miraculous) results of this breakthrough innovation, CAR-T has gathered so much interest among professionals that most of them are looking to set it up in medical centers across the country.

How CAR-T Therapy Works

A form of biologic or immunotherapy, the CAR T-cell method uses the body’s immune system to fight cancer cells, especially those present in the blood.⁴ Over the past year, the different types of cancers and conditions that this therapy can treat has only increased.

The process is multi-step — screening and evaluation of patients, the collection of blood by leukapheresis, genetic engineering of T-cells with the CAR gene, multiplication, conditioning therapy, IV infusion, and finally, recovery of patients — and is often, time-consuming. Following the procedure, there could be re-admittances to monitor treatment response and address side effects, if any, but the well-reputed programs ensure patient safety throughout the period.^4,6

Doctors and medical specialists have jumped onboard the CAR-T bandwagon in the recent months due to its staggering success with incurable cancers. As Stephan A. Grupp of the Children’s Hospital of Philadelphia mentioned, “If we can see it work in acute myeloid leukemia or even solid tumors, then my optimism about this being paradigm shifting is warranted.”⁵

On the other hand, to start and establish a practice with CAR T-cell therapy has been a grey area for the industry, that if left ambiguous, could in the long-run, disrupt access to eligible patients.

Logistics of a CAR-T Program

Accreditations

As of May 2018, there are a few certified medical centers (e.g., Massachusetts General Hospital, Dana Farber Cancer Center) that are allowed to administer CAR-T to eligible patients, although not all institutions are approved for both Kymriah and Yescarta. Meanwhile, professional organizations like the Foundation for the Accreditation of Cell Therapy (FACT) are working to develop a set of guidelines to ensure defined standards, and thus, safe and effective delivery of the therapy.⁷ It is also interesting to note that the FDA has mandated Risk Evaluation & Mitigation Strategies (REMS) for providers, in approving CAR T-cell-based products, which essentially ensures appropriate toxicity management.⁸

Infrastructure & Feasibility

As explained by Navneet, S. Majhail of the Cleveland Clinic in Ohio, most clinics conducting regular blood and marrow transplantation may not face feasibility issues in terms of basic infrastructure and quality processes as both these techniques follow a similar model. But some experts believe that, initially, CAR T-cell therapy should be performed in transplant centers that possess experience in clinical trials of the product. Dr. Majhail also expressed the need for the provision of coding infrastructure to overcome complications like cytokine-releasing syndrome.⁸

Insurance & Costs

A heavily debated topic that has, in the past, played spoilsport and even divided the industry on the issue, is the cost of the program for payers as well as the institutions themselves. For instance, the list price of Yescarta is $373,000 just for the drug, not taking into account labor charges, hospital stay, and other costs.⁹ While only a select population of the United States can afford such enormous amounts, some medical centers themselves are not open to the idea of implementing CAR-T programs without guarantees from Medicare. Memorial Sloan Kettering, a large hospital with a reputed cancer care center, has admitted to taking a risk by introducing the product and indicate that they will reassess if the financial risk becomes too high.⁵ Then again, it also is of the popular belief that if more companies invest in this cell therapy, the price may drop.⁸

Some other aspects of designing a suitable CAR-T program, worth mentioning, are the education of oncologists in deciding whether or not to refer or treat patients by this method, success rates, creating awareness among patients, and the role of allogeneic transplant in CAR T-cell therapy.

References