Discussion
LBCL
DISEASE, REMISSIONS
Patients with LBCL who are refractory or who relapse early after first-line chemoimmunotherapy are often chemorefractory and have a very limited cure rate after standard chemoimmunotherapyIn this patient population with poor prognostic features, including 54.8% with primary refractory disease and 63.4% who were refractory to bridging therapy, treatment with axi-cel resulted in high response rates and durable remissions. The investigator-assessed best ORR and best CMR were 90.3% and 79.0%, respectively. Median PFS was 11.8 months and median OS was not reached. Furthermore, the efficacy of axi-cel was maintained across key subgroups, including patients with high-risk features, such as age ≥70 years, HCT-CI score ≥3, IPI ≥ 3 and primary refractory disease. The only exception was in patients with a high TMTV at inclusion, as we observed a reduced CMR at 3 months among these patients. This observation is consistent with other studies evaluating CAR-T cell therapy for R/R LBCL, in which a high TMTV was associated with an increased risk of early relapse or progressionThe findings of ALYCANTE are overall consistent with the results of the phase 3 ZUMA-7 trialAnother CD19-directed CAR-T cell product, lisocabtagene maraleucel (liso-cel), has also been evaluated as a second-line therapy in the open-label, phase 2 PILOT study performed in 61 patients with R/R LBCL who are ineligible for ASCTDespite the comparable study designs and sample sizes of ALYCANTE and PILOTCurrently, there are no standard criteria nor consensus to determine whether a patient can undergo HDCT/ASCT. In most countries, a theoretical age limit for HDCT/ASCT is set to 65–70 years. The age cutoff to define ASCT ineligibility differed between ALYCANTE (65 years) and PILOT (70 years); however, in the present study, subgroup analysis demonstrated that efficacy and safety outcomes after axi-cel infusion were overall similar between patients aged <70 years and ≥70 years. Numerous investigations have additionally found that HCT-CI, a well-established prognostic model for comorbidities, can predict survival outcomes for both autologous and allogeneic stem cell transplantationThis study is limited by its single-arm design with no active control group. Therefore, selection bias cannot be ruled out. Although axi-cel compares favorably to second-line chemoimmunotherapy based on historical controlsIn conclusion, axi-cel as a second-line treatment resulted in high response rates and durable remissions in patients with high-risk R/R LBCL with poor prognostic features and who were not eligible for HDCT/ASCT. Moreover, despite advanced age and comorbidities, axi-cel had an acceptable safety profile in this population considered unfit for HDCT/ASCT. Together, these results support axi-cel as a second-line treatment in patients with R/R LBCL who are deemed ineligible for HDCT/ASCT.