Axi-Cel Continues to Demonstrate Durable Responses for Patients With R/R Large B-Cell Lymphoma

5-Year Follow-Up Data from the US Lymphoma CAR-T Consortium

According to 5-year follow-up data from the US Lymphoma CAR-T Consortium, the autologous CD19 chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel), approved for the treatment of relapsed or refractory (R/R) large B-cell lymphoma, demonstrated continuous sustained, durable responses among patients with large B-cell lymphoma as standard-of-care. However, late infections and subsequent malignant neoplasms (SMNs) showed the potential to develop and impact long-term survival, particularly among elderly patients.

Investigators previously reported trial results of 298 patients who underwent leukapheresis with the intent to receive standard-of-care axi-cel (n = 275 infused) after 2 or more previous lines of therapy at a median follow-up of 12.9 months. Current results report on an extended follow-up of this cohort to a median of 58 months, particularly focusing on late survivorship events.

Updated results demonstrate that among patients who were treated with axi-cel, progression-free survival (PFS) at 5 years was 29% and overall survival (OS) at 5 years was 40%. The 5-year lymphoma-specific survival was 53% with infrequent late relapses. However, the 5-year non-relapse mortality (NRM) was 16.2%, as investigators noted that over half of NRM events occurred beyond 2 years.

Study authors noted patients who were 60+ years had a lower risk of relapse (P = .02) but exhibited a higher risk of NRM compared with patients younger than 60 years (NRM odds ratio, 4.5 [95% [confidence interval] CI, 2.1 to 10.8]; P < .001). It was observed that late NRM was mostly due to infections and SMNs. Overall, SMNs occurred in 24 patients (9%), including therapy-related myeloid neoplasms (n = 15), solid tumors (n = 7), and unrelated lymphoid malignancies (n = 2).

“In the standard-of-care setting, axi-cel exhibits outcomes consistent with those reported in clinical trials, with sustained, durable responses observed at the 5-year time point. However, late infections and the development of SMN are key survivorship issues that reduce long-term survival after CAR T-cell therapy, particularly in the elderly,” concluded lead study author Michael Jain, MD, PhD, Moffitt Cancer Center, Tampa, Florida, and colleagues.

Source:

Jain M, Spiegel J, Nastoupil L, et al. Five-year follow-up of standard-of-care axicabtagene ciloleucel for large b-cell lymphoma: Results from the US lymphoma CAR T consortium. J Clin Oncol. Published online August 2, 2024. doi: 10.1200/JCO.23.02786