Axicabtagene ciloleucel (axi-cel), a CAR T-cell therapy, has demonstrated a significant overall survival (OS) advantage compared to standard of care in elderly patients (≥65 years) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). This finding comes from a subgroup analysis of the phase 3 ZUMA-7 trial, presented at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition, and offers a potentially curative second-line treatment option for this patient population.
The subgroup analysis included 109 patients aged 65 and older. Results showed a median OS of 43.5 months (95% CI; 20.9-NE) in patients receiving axi-cel compared to 19.5 months (95% CI; 12.3-NE) in those receiving standard of care (HR, 0.691; 95% CI, 0.401-1.190). Among patients aged 70 years and older, the median OS was 24.7 months (95% CI; 12.8-NE) with axi-cel versus 11.2 months (95% CI; 6.1-NE) with standard of care (HR, 0.330; 95% CI, 0.135-0.809).
Progression-Free Survival
Axi-cel also demonstrated a marked improvement in progression-free survival (PFS) in the older patient subgroup. The median PFS in patients aged 65 and older was 28.6 months (95% CI; 5.1-NE) with axi-cel compared to 5.0 months (95% CI; 2.8-7.3) with standard of care (HR, 0.406; 95% CI, 0.230-0.715). In patients 70 years and older, the median PFS was 11.4 months (95% CI; 4.1-NE) and 2.7 months (95% CI; 1.7-5.0) in the axi-cel and standard of care arms, respectively (HR, 0.206; 95% CI, 0.078-0.547).
Expert Commentary
"In the subgroup analysis, axi-cel as second-line therapy showed prolonged survival over standard of care in patients aged 65 years or older, including in patients aged 70 years or older," said Marie José Kersten, MD, professor of hematology at Amsterdam University Medical Centers, who presented the data. "These findings confirm that age alone should not be a barrier for consideration of CAR T-cell therapy and support the use of axi-cel as a curative intense second-line therapeutic option for elderly patients with relapsed refractory large B-cell lymphoma."
Trial Design
The international phase 3 ZUMA-7 trial randomized patients with refractory LBCL who had relapsed within 12 months of first-line chemoimmunotherapy to either axi-cel or standard of care, followed by high-dose chemotherapy with autologous stem-cell transplantation for those responding to chemoimmunotherapy. Patients who did not respond to standard of care were allowed to receive cellular immunotherapy. The primary endpoint was event-free survival (EFS), with secondary endpoints including OS, PFS, and safety.
Adverse Events
While axi-cel demonstrated significant efficacy, adverse events (AEs) were also observed. Any-grade and grade 3 or higher AEs of interest in the axi-cel arm versus the control arm included cytokine release syndrome (98% and 8% vs NE), neurological events (67% and 27% vs 25% and 2%), hypogammaglobulinemia (20% and 0% vs 2% and 0%), cytopenia (84% and 84% vs 82% and 76%), and infections (61% and 29% vs 38% and 16%). Death occurred in 51% of patients receiving axi-cel and 53% of patients receiving standard of care, primarily due to progressive disease.
Naive T Cells
Interestingly, improved OS in patients 65 years and older who received axi-cel was associated with a greater proportion of naive T cells (HR, 0.369; 95% CI, 0.138-0.984), suggesting a potential biomarker for treatment response in this population.
