Dr Nayak on the Investigation of Axi-Cel in CNS Lymphoma

Lakshmi Nayak, MD, director, Center for Central Nervous System (CNS) Lymphoma, senior physician, Dana-Farber Cancer Institute; associate professor, neurology, Harvard Medical School, discusses the investigation of axicabtagene ciloleucel (Yescarta; axi-cel) in a pilot study for patients with relapsed/refractory primary and secondary CNS lymphoma.

Notably, findings from this investigation were presented at the 2024 ASCO Annual Meeting. The study concluded that axi-cel is both safe and effective in treating patients with these diseases, with no increased risk of immune effector cell-associated neurotoxicity syndrome (ICANS) compared with in systemic diffuse large B-cell lymphoma (DLBCL). At a median follow-up of 24 months, the median progression-free survival was 14.3 months (95% CI, 6.3-not reached [NR]), with an overall response rate of 94% and a complete response rate of 67%. Despite the high relapse rates typically associated with current CNS lymphoma treatments, axi-cel was effective and durable in this patient population. The median duration of response was 13.4 months (range, 1-30), and the median overall survival was 26.4 months (95% CI, 11.2-NR).

Cytokine release syndrome (CRS) occurred in 89% of patients, primarily at low grades, and ICANS occurred in 44% of patients, with 28% of patients experiencing grade 3 ICANS.

Axi-cel, which is a CD19-directed CAR T-cell therapy, has transformed the treatment of patients with relapsed/refractory systemic DLBCL, Nayak begins. Axi-cel is FDA-approved in the second- and third-line settings for the treatment of patients with large B-cell lymphoma, she says. Notably, this regulatory decision was based on findings from the phase 3 ZUMA-7 trial (NCT03391466). However, initial studies investigating this agent in systemic DLBCL excluded patients with CNS lymphoma, leaving the safety and efficacy of axi-cel in this patient subgroup unclear, Nayak emphasizes.

This pilot study was therefore conducted to primarily assess the safety of axi-cel in patients with CNS lymphoma, with additional end points comparing the incidence of adverse effects with this treatment in patients with CNS lymphoma to the incidence of those in other patient populations, she says. Additionally, as a secondary end point, the study evaluated the efficacy of axi-cel in this difficult-to-treat patient subgroup, Nayak concludes.