Objective  To analyze real-word experience of patients with relapsed/refractory large B-cell lymphoma (LBCL) after failure of chimeric antigen receptor-T (CAR-T) cell therapy.

  Methods  We retrospectively evaluated clinical outcomes and salvage therapies from 16 patients who relapsed or progressed following CD19 CAR-T cell therapy at The First Affiliated Hospital of Nanchang University between July 2018 and December 2022.

  Results  The cohort had 10 males and 6 females, with a median age of 53.5 years (range, 16-72).The prognosis of these patients was extremely poor, with a median overall survival (mOS) of only 5.7 months (95% confidence interval CI: 5.1-6.3). Compared with supportive or palliative care exhibiting a mOS of 2.1 months (n=4, 95%CI: 0–4.8), subsequent antitumor therapies (n=12) were associated with a statistically significant survival benefit, with a mOS of 9.8 months (95%CI: 3.3–16.3, P<0.05). Next-line antitumor regimens included Pola-BR (n=4, 33.3%), BTK inhibitor (n=4, 33.3%), anti-PD-1 antibody (n=2, 16.7%), and conventional immune-chemotherapy (n=2, 16.7%), witha partial response observed in four patients (33.3%). For the BTK inhibitor- based treatment, two cases (50%) exhibited a partial response, and the mOS was 10.8 months (95% CI: 3.4-18.1), which showed a trend of superiority compared with the other regimens (P>0.05).

  Conclusions   CAR-T cell therapy failure demonstrated a very poor prognosis and the treatment options were very limited for patients with LBCL. Further research is needed to determine the optimal salvage regimen following failure of CAR-T cell therapy.