Study to Evaluate the Efficacy of Axicabtagene Ciloleucel in Patients With Late Relapse of Diffuse Large B-Cell Lymphoma

Single-arm, open-label, multicenter, phase II trial aiming to include approximately 45 patients over 24 months. Patients will receive axicabtagene ciloleucel infusion and will be followed up to 5 years. The total duration of the study is therefore of 7 years.

Axicabtagene Ciloleucel , an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated a high rate of durable responses with a manageable safety profile, in patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more previous therapies. Recently, axicabtagene ciloleucel as demonstrated superior efficacy compared to standard of care (SOC) in 2nd line LBCL patients considered eligible for autologous stem-cell transplantation (ASCT) with primary refractory disease or early relapse (ZUMA-7). In this study, after a median follow-up of 24.9 months, the median event-free survival was 8.3 months in the axicabtagene ciloleucel group and 2.0 months in the standard-care group, and the 24-month event-free survival was 41% and 16%, respectively (hazard ratio, \[HR\] for event or death, 0.40; 95% confidence interval, 0.31 to 0.51; p\<0.001). Some response occurred in 83% of the patients in the axicabtagene ciloleucel group and in 50% of those in the SOC group (with a complete response \[CR\] in 65% and 32% of the patients, respectively). These data led to the approval of axicabtagene ciloleucel by the American and European regulatory agencies, for patients with LBCL refractory to first-line or relapsing within the first year after completion of induction immunochemotherapy. More recently, the open-label phase 2 ALYCANTE trial assessed the safety and efficacy of axicabtagene ciloleucel as second-line therapy in patients with primary refractory or early relapsed aggressive B-cell lymphoma who were not deemed candidates for ASCT. Treatment with axicabtagene ciloleucel resulted in high response rates (best overall response 92.5%, best CR = 80.0%) and durable remissions (median PFS, 11 months, median overall survival \[OS\], not reached), with an acceptable safety profile in this population of patients considered unfit for ASCT. The above-mentioned trials included only patients who were primary refractory or had relapsed within a year of completing first-line treatment. However, no data are available on the efficacy of axicabtagene ciloleucel in second line for patients relapsing more than one year after completion of induction. Although it is generally assumed that the outcome of these patients is better than that of patients showing early failure, still the outcome is not optimal at all, with at least half of the patients dying from the lymphoma in the next months. The current proposal is aimed at studying a possible role of axicabtagene ciloleucel in this subset of cases.