A phase 2 study published in Nature Medicine supports the use of axicabtagene ciloleucel (axi-cel; Yescarta) as a second-line therapy for patients with relapsed or refractory large B-cell lymphoma (LBCL) who are not eligible for autologous stem cell transplant (ASCT). The trial demonstrated promising efficacy and a manageable safety profile, offering a potential new treatment option for this patient population.
The study met its primary endpoint, achieving a complete metabolic response (CMR) rate of 71.0% (95% CI, 58.1%-81.8%) at 3 months. After a median follow-up of 12.0 months (range, 2.1-17.9), the median progression-free survival (PFS) was 11.8 months (95% CI, 8.4-not reached). Overall survival (OS) was not reached during the follow-up period.
Efficacy and Safety Outcomes
The investigator-assessed objective response rate (ORR) at 3 months was 75.8% (95% CI, 63.3%-85.8%). At 6 months, 59.7% of patients (n = 37) remained in CMR (95% CI, 46.5%-72.0%). The best ORR and CMR, as assessed by investigators, were 90.3% and 79.0%, respectively. Central review panel assessments showed similar results, with a CMR of 66.1% and an ORR of 69.4% at 3 months. The best ORR and CMR by central review were 91.9% and 82.3%, respectively. Median event-free survival (EFS) was 12.3 months (95% CI, 7.2-NR) at 12 months, and median duration of response (DOR) was not reached.
Regarding safety, all patients experienced adverse events (AEs) of any grade, with 95.2% (n = 59) experiencing grade 3 or higher AEs. The most common grade 3 or higher AEs were neutropenia (66.1%), anemia (38.7%), and thrombocytopenia (38.7%). Any-grade infections were reported in 53.2% (n = 33) of patients. Grade 3-4 cytokine release syndrome (CRS) and neurologic events (NEs) occurred in 8.1% and 14.5% of patients who received axi-cel, respectively. Notably, no deaths were attributed to either CRS or NEs.
Study Design and Patient Characteristics
The prospective, multicenter, open-label, phase 2 trial enrolled 69 patients, with 62 receiving an axi-cel infusion. The median patient age was 70 years (range, 49-81), and 24.2% were female. The majority (98.4%) had an ECOG performance status of 0 or 1. Over half (54.8%) had disease refractory to first-line chemoimmunotherapy. Most patients (88.4%) were deemed ineligible for ASCT due to age, while 32.3% had a high hematopoietic cell transplantation-specific comorbidity index and/or had previously undergone ASCT.
Broader Context and Future Directions
"In this prospective, multicenter, open-label, phase 2 trial, a single axi-cel infusion was associated with a manageable safety profile and a high antitumor activity. The study met its primary end point with a CMR at 3 months of 71% versus 12% with [standard-of-care] (second-line chemoimmunotherapy) based on historical controls," the study authors wrote.
These findings are further supported by data presented at the American Society of Hematology Annual Meeting & Exposition in December 2023. The phase 2 ZUMA-12 trial demonstrated a complete response rate of 86% when axi-cel was administered as a first-line treatment in patients with high-risk LBCL. Additionally, in patients aged 65 or older with second-line LBCL, axi-cel improved OS and PFS compared with standard-of-care in the phase 3 ZUMA-7 trial.
Investigators plan to continue evaluating secondary endpoints, including health-related quality of life, cell product characteristics, and cellular kinetics of axi-cel.
