Axicabtagene Ciloleucel Safe and Tolerable for Relapsed, Refractory Central Nervous System Lymphoma


Participants in the study had durable response for over 1 year, in addition to positive efficacy indicators.

Axicabtagene ciloleucel (Yescarta, axi-cel; Kite), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, was deemed to be safe and tolerable in patients with relapsed/refractory (R/R) central nervous system lymphoma (CNSL), in addition to having positive efficacy markers and a durable response for over 1 year, according to study results published in the Journal of Clinical Oncology.1

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The data, which were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, could be key to developing effective treatment options for patients with CNSL. The prognosis for these patients is typically poor, and there are no standard of care treatment options available.

Previous literature has been published indicating axi-cel’s effectiveness when treating a different type of lymphoma, R/R large B-cell lymphoma (LBCL). One study found that axi-cel as a second-line treatment for patients with R/R LBCL led to significantly longer overall survival than standard care at a median follow-up of 47.2 months.2

Such literature has guided the authors of the current study in their belief that axi-cel could be considered for treating patients with CNSL, thus filling an important gap in care for these patients.

There were 18 patients enrolled in the study, and the first 6 underwent further observation to locate any treatment-limiting toxicities (TLTs). The primary end point of the study was safety, which was measured by the rate of TLTs and any adverse events at grade 3 or higher, according to the investigators. Secondary end points included complete response (CR) rate, duration of response (DOR), objective response rate (ORR), overall survival (OS), and progression-free survival (PFS).

The median age of the study participants was 62 years (range: 33 to 80), and 8 of the 18 patients were women. The median number of prior therapies patients had undergone was 3 (range: 1 to 7). Importantly, no TLTs were observed.

Despite the lack of TLTs, other effects impacted some of the patients. Sixteen of the 18 patients (89%) developed cytokine release syndrome (CRS), but none of them developed it at grade 3 or higher. Additionally, 8 of the 18 participants developed immune effector cell-associated neurologic syndrome (ICANS) (44%), with 5 of them (28%) at grade 3 or higher.

ORR was found to be 94% (17/18), while the CR was 67% (12/18), the investigators wrote. Furthermore, as of January 2024, the median follow up was 24.2 months, the median DOR was 13.4 months, and 9 patients had progressed. Median PFS was 14.3 months (95% CI: 6.3-NR), while median OS was 26.4 months (95% CI: 11.2-NR). Seven patients have died from disease progression.

About the Trial

Trial Name: Axi-cel in CNS Lymphoma Identifier: NCT04608487

Sponsor: Dana-Farber Cancer Institute

Estimated Completion Date: June 1, 2025

The investigators noted that, at the time of presentation at ASCO, there was be a minimum follow-up of 12 months, and that correlative data for all 18 patients was presented at the annual meeting.

Interestingly, the pharmacokinetics of axi-cel in the first 12 patients with CNSL were similar to previously reported results in the ZUMA-1 and ZUMA-7 trials for patients with diffuse large B-cell lymphoma without any central nervous system involvement.

In the ZUMA-1 study, the ORR rate among the 111 patients enrolled in the study was 82%, and the CR was 54%. Additionally, 42% of patients continued to have a response at the median follow-up point, and there was a similar presence of CRS, although in this study 13% of those with CRS developed it at grade 3 or higher.3

Overall, the investigators concluded that, “Axi-cel was safe and well-tolerated in CNSL patients with encouraging efficacy and median PFS and durability of response of more than 1 year,” with no obvious risk of adverse neurological effects.

1. Nayak L, Chukwueke U N, Meehan C, et al. A pilot study of axicabtagene ciloleucel (axi-cel) for relapsed/refractory primary and secondary central nervous system lymphoma (PCNSL and SCNSL). J Clin Oncol. 2024;42(16). doi:10.1200/JCO.2024.42.16_suppl.2006
2. Westin J, Oluwole O, Kersten M, et al. Survival with axicabtagene ciloleucel in large B-cell lymphoma. N Engl J Med. 2023;389(2):148-157. doi:10.1056/NEJMoa2301665
3. Neelapu S, Locke F, Bartlett N, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(36):2531-2544. doi:10.1056/NEJMoa1707447
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