Working Toward CAR T-Cell Treatments With Fewer Side Effects

Having worked with pharmaceutical companies that are producing chimeric antigen receptor (CAR) T-cells for treatment of several cancers, Loyola University Chicago and Loyola Medicine announced plans this week to take the next step and develop their own cells.

Supported by the Leukemia Research Foundation, Loyola seeks to develop cells that can be used by other cancer treatment centers in Chicago. "We're working to develop a purer CAR-T product that would lessen toxic side effects and potentially increase the number of eligible patients," said Patrick Stiff, MD, Loyola's director of hematology/oncology research and division director of hematology/oncology.

Kevin Radelet, executive director of the Leukemia Research Foundation, said supporting CAR-T research "directly aligns with our mission of funding medical research and enriching the quality of life of those touched by these diseases."

In the CAR T-cell therapy process, a patient’s own T-cells are removed and then genetically altered in a process that can take several weeks. While CAR T-cell therapy has cured certain leukemias and lymphomas in clinical trials and commercial settings, side effects can be serious. These can include high fevers and low pressure after administration, known as cytokine release syndrome, as well as neurotoxicity in the brain.

Developing a CAR T-cell therapy with fewer side effects could have implications for reimbursement. On August 22, 2018, the Medicare Evidence Development and Coverage Advisory Commission (MEDCAC), mostly endorsed including patient-reported outcomes in a final national coverage analysis, which will come sometime in 2019.

What MEDCAC panelists say about CAR T-cell therapy.

When the first CAR T-cell therapy, tisagenlecleucel (Kymriah) was approved in 2017, Novartis thought it had reached a value-based agreement with CMS, but since then UnitedHealthcare asked for a National Coverage Determination, a move supported by other payers. Tisagenlecleucel costs $475,000 for a 1-time treatment, and Gilead’s axicabtagene ciloleucel, or axi-cel, (Yescarta) costs $373,000. Both these prices do not include the cost of administering the treatment, which can bring total costs to $1 million.

Loyola University Medical Center took part in ZUMA-1, the clinical trial of axi-cel presented last December at the American Society of Hematology and published in the New England Journal of Medicine. The multicenter study included patients with certain types of large B-cell lymphoma who had failed standard treatments. After 15 months, 42% were in complete remission, a result that came after most of the patients had failed on other treatments. However, the study found that 95% of the patients experienced at least 1 severe side effect.

Loyola officials noted that Medicare patients account for 50% of the lymphoma population; reducing side effects could allow some to be treated in outpatient settings, which would bring down treatment costs. Side effects are a key reason only specialized, approved cancer centers are authorized to administer CAR T-cell treatments.

By producing a less toxic product, it may be possible to move the expensive inpatient therapy to an outpatient setting. This could allow many more patients to be treated, including Medicare patients who comprise approximately 50% of the lymphoma population.

Loyola initially will test its CAR T cells on patients with acute lymphocytic leukemia and B-cell non-Hodgkin lymphoma who have failed standard treatments.