ASCO 2024 | A pilot study of axi-cel in primary and secondary CNS lymphomas

So relapsed and refractory primary and secondary CNS lymphomas are a major unmet need in oncology. Presently, axi-cel or axicabtagene ciloleucel has been found to be very efficacious and has led to FDA approval in second line therapy as well as third line therapy in diffuse large B cell lymphoma. However, CNS lymphomas in these initial studies that investigated the role of axi-cel in systemic diffuse large B cell lymphoma excluded any patients with known CNS involvement or prior CNS disease. Specifically, primary CNS lymphoma is an absolute exception to the label.

So we conducted this study, this pilot study to investigate the safety of axi-cel in central nervous system lymphomas, and then also to evaluate the efficacy. So one of the concerns that people have questioned about is if CD19 directed CAR-T cell therapy and in this case, axi-cel would be safe in CNS lymphomas. One of the side effects that have been noted with CD19 directed CAR-T cell therapy have been ICANS or neurotoxicity related to cellular therapies, and that has been a question whether patients with brain tumors would have more side effects in that regard.

So the primary endpoint of our study was to see if this was safe, and also to evaluate whether more patients would suffer from such side effects. And then the secondary endpoints included, of course, efficacy that included the response rates, duration of response, progression free survival, overall survival. And then we also wanted to evaluate from a correlative standpoint if axi-cel gets into the brain. And also, we wanted to evaluate the CAR-T cells in the spinal fluid and compare them to the peripheral blood and be able to determine mechanisms of resistance and response to the therapy and also mechanisms of neurotoxicity in this setup. What we found is in our study that axi-cel was extremely safe, and the incidence of cytokine release syndrome and the neurotoxicity or ICANS was similar to that noted in the initial systemic diffuse large B cell lymphoma studies. So that was fantastic. We did not encounter any different safety signal. And we found that this drug is or this compound is very safe in our patient population.

Importantly, what we noted was the efficacy. We found a remarkable response rate of 94% in our patient population, of course, this is a small cohort of 18 patients. Nonetheless, this was very great to see and the complete response rate was 67%. Additionally, we noted not only that we saw responses, but these were durable responses. And this was what was very striking to me as an oncologist who treats these patients, we are seeing several targeted therapies and novel therapies that have a reasonable response rate. However, the durability is quite short in all of the studies that have been published so far. In our study, we found that the median progression free survival in our 18 patient cohort was 14 months. So this is very spectacular for this extremely aggressive brain tumor to find not just such high evidence of efficacy, but also remarkable durability.