The chimeric antigen receptor T-cell (CAR-T) therapies axicabtagene ciloleucel (axi-cel; Yescarta®) and tisagenlecleucel (tisa-cel; Kymriah®) have overlapping indications for some types of relapsed/refractory aggressive B-cell lymphomas, yet there is little data comparing the efficacy, safety, and patterns of use between the 2 products.
New research presented at the annual Transplantation and Cellular Therapy Meetings of ASCT and CIBMTR in February 2020 examined data collected from 8 treatment centers, which had the option of prescribing either CAR-T cell therapy for relapsed/refractory B-cell lymphoma.1
“One of the questions that we were trying to understand was: What are some of the practice patterns in centers that essentially have the option of prescribing either product?” explained Peter Riedell, MD, assistant professor of medicine at the University of Chicago Medicine center (UChicago Medicine) and a lead author of the research. “And additionally, along those same lines, we wanted to try to get a better sense of what the efficacy and safety of these 2 agents were in the real-world setting.”
The data was collected from 242 individuals who underwent apheresis for axi-cel (67% of patients) or tisa-cel (33% of patients) from May 2018 through July 2019, and the vast majority were diagnosed with diffuse large B-cell lymphoma. Researchers reported that 7% of those who were to receive axi-cel and 9% of those who were slated to receive tisa-cel died prior to CAR-T infusion as a result of lymphoma progression.
One big difference between the axi-cel and the tisa-cel recipients was the state of their disease — 45% of axi-cel patients had primary refractory disease, compared with 18% of tisa-cel patients. One possible reason for this is tisa-cel’s comparatively longer manufacturing time: the median vein-to-vein time of axi-cel was 28 days, compared with 44 days for tisa-cel.
“If you have a patient that you’re seeing in clinic who has really rapidly progressive disease, you probably aren’t able to wait that time frame to get the product back,” Dr Riedell explained. Patients who received tisa-cel were also more likely to receive bridging therapies “to temporize their disease,” he added.
The study also documented differences in resource utilization between the 2 products. The patients who received axi-cel tended to be hospitalized for longer compared with those treated with tisa-cel, and had a higher likelihood of being transferred to intensive care units.
Patients who received tisa-cel also tended to be much older than those who received axi-cel. The median age at apheresis was 67 years, compared with a median patient age of 59 years for axi-cel. Dr Riedell added, “62% of our patients who received tisa-cel were aged 65 or older, compared to only 34% of patients who received axi-cel,” Dr Riedell added.
Dennis Cooper, MD, professor of medicine and chief of blood and bone marrow transplantation at Rutgers Cancer Institute of New Jersey, who was not involved in the research, suggested one possible reason for this trend: “There’s really no way to give the axi-cel as an outpatient.” The product is almost universally given in the inpatient setting because of the short onset and severity of cytokine release syndrome (CRS), whereas tisa-cel, which appears to cause less severe CRS with slightly longer time to onset, can be administered in the outpatient setting — and products used in this setting are typically reimbursed more favorably.
According to the data, 93% of patients who received axi-cel received it as an inpatient, compared with 37% for tisa-cel patients. “The problem with that is if you give axi-cel to a Medicare patient, then you’re going to lose a lot of money. So I think that at some institutions, they may prioritize the tisa-cel in patients who are [of] Medicare age, because that one can be given as an outpatient [treatment].”