Axicabtagene ciloleucel (axi-cel) has shown promising results as a second-line therapy for patients with aggressive B-cell lymphoma who are ineligible for high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT). A recent study published in Nature Medicine evaluated the efficacy and safety of axi-cel in this patient population, demonstrating a high complete metabolic response rate and manageable safety profile.
The study enrolled 69 patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma, with 62 receiving a single infusion of axi-cel. The primary endpoint was investigator-assessed complete metabolic response (CMR) at 3 months post-infusion. Secondary endpoints included objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), and the incidence of adverse events.
Efficacy Outcomes
The study met its primary endpoint, with a CMR of 71.0% (95% CI, 58.1-81.8%) at 3 months. The investigator-assessed ORR at 3 months was 75.8% (95% CI, 63.3-85.8%). At a median follow-up of 12 months, the median EFS from leukapheresis was 12.3 months (95% CI, 7.2-not reached), and the estimated EFS rates at 6 and 12 months were 66.7% and 51.2%, respectively. Median PFS from axi-cel infusion was 11.8 months (95% CI, 8.4-not reached), with estimated PFS rates at 6 and 12 months of 67.7% and 48.8%, respectively. The median OS was not reached, with estimated OS rates at 6 and 12 months of 91.9% and 78.3%, respectively.
Safety Profile
All patients experienced at least one adverse event of any grade. Grade 3 or higher adverse events occurred in 95.2% of patients, with the most common being neutropenia (66.1%), anemia (38.7%), and thrombocytopenia (38.7%). Cytokine release syndrome (CRS) occurred in 93.5% of patients, with grade 3 or higher CRS reported in 8.1%. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 51.6% of patients, with grade 3 or higher ICANS reported in 14.5%. CAR-T cell toxicities were managed with tocilizumab (77.4%) and/or corticosteroids (64.5%). Non-relapse mortality (NRM) was recorded in 9.7% of patients, with fatal adverse events occurring late and primarily due to infections.
Subgroup Analysis
Subgroup analyses indicated that the efficacy and safety of axi-cel were consistent across different patient populations, including those aged ≥70 years and those with comorbidities (HCT-CI score ≥3). Patients aged ≥70 years did not show increased toxicity compared to younger patients. However, a high total metabolic tumor volume (>80 ml) at inclusion was associated with a reduced CMR at 3 months.
Clinical Implications
These results suggest that axicabtagene ciloleucel is an effective second-line treatment option for patients with aggressive B-cell lymphoma who are ineligible for HDCT/ASCT. The manageable safety profile and promising survival outcomes support its use in this patient population, including older patients and those with comorbidities. Further research is needed to optimize patient selection and management strategies to maximize the benefits of axi-cel therapy.
