ASCO21: Current Issues with CAR T Cells for Hematologic Malignancies

At the 2021 virtual ASCO Annual Meeting, Saar Gill, Jeffery Tice, and Jennifer Brudno spoke about the recent advances and challenges surrounding CAR T cells for hematologic malignancies.

Hematologic malignancies are a diverse collection of cancers that affect the blood, bone marrow, and lymph node. It is estimated to affect ~180,000 people and result in ~57,00 deaths in the US annually. Most complications with this disease arise when patients do not respond to standard chemotherapy or/and when their disease reoccurs. CAR T cell-based therapies have shown to be effective under these difficult to treat conditions. CAR T cells are a form of immunotherapy where patients’ immune cells are engineered to treat their cancers.

In his talk, Dr. Gill highlighted that in just the last 4 years, five new commercial CAR T cell products have been developed. These have been tested in children and adults with relapsed and refractory leukemias, lymphomas, and myelomas and showed promising results. In these studies, CAR T cells improved the overall survival for patients without additional therapy, however, the therapy did result in severe side effects.

Dr. Saar Gill, University of Pennsylvania

Dr. Gill noted that as there have not been large randomized clinical trials comparing these five CAR T cells therapies to each other and to standard chemotherapies. Thus, a current challenge is identifying the advantages and differences between CAR T cell therapies and identifying their potential as a first-line treatment.

Dr. Tice focused on the financial barriers to market access for CAR T cells. According to the institute for clinical and economic review (ICER), the incremental cost-effectiveness threshold for a given therapy is between 50,000 – 150,000$ in the US. As an example, he showed that patients with multiple myeloma who received idacabtagene vicleucel (CAR T cell therapy) had a high certainty of at least a small net health benefit, possibly substantial.

Dr. Jeffery Tice, UCSF

However, the cost-effectiveness of the treatment was 319,000$, highlighting that CAR T cells are not cost-effective at current prices. Additional barriers include limited availability of the treatment at centers, insurance barriers, and inadequate reimbursement, which would likely exacerbate disparities in care. Dr. Tice suggested that current list prices would need to be reduced by at least 37% to approach reasonable to pay thresholds in the US.

Finally, Dr. Jennifer Brudno presented the CAR T cell toxicities. The most common toxicities are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which present at high rates in patients who received CAR T cells. Fortunately, there are treatment options for both toxicities, including treatment with tocilizumab and corticosteroids.

Dr. Jennifer Brudno, National Cancer Institute

Dr. Gill presented promising clinical data for CAR T cell therapy in several hematologic malignancies. The side effects for current therapies are severe, as is usual with anti-cancer treatments, however, according to Dr. Brudno, these adverse events can be managed. While CAR T cells have shown encouraging results in the clinic, the efficacy of this therapy has not been extensively tested in hematologic malignancies with lower survival rates.

Furthermore, at current prices, CAR T cell treatments are most likely not available to most people due to their low-cost effectiveness score. With all these issues, the speakers were confident in the future of CAR T cell therapies. As with time and more knowledge, these barriers will hopefully be overcome, and CAR T cell therapy could be available to more patients.

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Nicole Bata