Andre Goy, MD
Adding to the excitement of the FDA’s August 2017 monumental approval of tisagenlecleucel (Kymriah) in acute lymphoblastic leukemia (ALL), the agency recently approved the CD19-directed chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel; Yescarta) as a treatment for adults with relapsed/refractory non-Hodgkin lymphoma (NHL).
, Andre Goy, MD, chairman and director, chief of Lymphoma, and director of Clinical and Translational Cancer Research at John Theurer Cancer Center, Hackensack Medical Center, discussed the recent success with CAR T-cell therapy, and what is on the horizon for this therapeutic option across hematologic malignancies.
OncLive: This year we had our first approved CAR T-cell therapy, and, more recently, another. Can you discuss what this means for the field?
The approval of tisagenlecleucel as the first CAR T cell approved in patients aged 13 to 25 years with relapsed/refractory ALL is a milestone in medicine well beyond oncology. This is the first approval of a live-cell, gene-modified therapy in the United States, and [is] a game changer.
Based on that, at our center, we will be opening a CAR T-cell unit. This is going to be a dedicated unit, as this treatment is a very difficult thing to manage in terms of toxicity.
How do you advise physicians in the community setting to take advantage of these options?
This is a very important question. The patients must be monitored in the context of a bone marrow or stem cell transplant unit with easy access to an intensive care unit (ICU), because many of these patients have severe complications.
In the ALL trial [of tisagenlecleucel], about 40% of patients had grade 3/4 cytokine release syndrome (CRS) toxicity and slightly a little less in the large cell lymphoma trial. What is happening is that there are 2 main types of toxicity.
The way this therapy works is that the T cells expand quite rapidly. The "cytokine storm" or CRS usually occurs within the first 2 to 3 days to the first 2 weeks. It consists of fever, cytopenia, or there could be hypertension or something that looks like sepsis—which we treat like a sepsis. Eventually, multiorgan failure occurs, as well. In the second aspect of toxicity is encephalopathy associated with CAR T cell; that can go from confusion to speech troubles and motor difficulty to eventually comatose and seizure. This usually occurs 1 to 2 weeks after CRS. This is again managed with supportive care and, obviously, steroids if needed. There is a clear correlation with the amplification of the T cells and neurological toxicity.
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