Long-Term Survival Following Relapse or Progression Post‒CAR-T in Patients with R/R LBCL Based on Real-World Data

Data on the long-term outcomes of patients who relapse or progress after CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy for third-line or later treatment of large B-cell lymphoma (LBCL) are limited. Findings from a German Lymphoma Alliance/German Stem Cell Transplantation Registry (GLA/DRST) real-world analysis (RWA) investigating characteristics, relapse patterns, and management strategies in patients with relapsed or refractory (R/R) LBCL surviving ≥1 year after failure of standard-of-care CAR-T therapy were reported at the 2022 European Hematology Association Congress.

The study sample consisted of 356 patients in a prior RWA after receipt of CAR-T therapy between November 2018 and April 2021 at 21 German centers; 173 patients received axicabtagene ciloleucel (axi-cel) while 183 received tisagenlecleucel (tisa-cel). Baseline characteristics, including patient, disease, and treatment features, were collected from MED-A cellular therapy forms. Centers were approached to provide additional treatment and follow-up information for each patient with a documented relapse or progression event.

Of the 356 patients in the original GLA/DRST study, 214 (60%) experienced relapse or a progression event after CAR-T therapy. For 143 of 214 patients (67%), full data sets as needed for the purpose of the study were available. Overall survival (OS) at 12 months following relapse or progression was 22%, with no significant difference between axi-cel and tisa-cel failures. Twenty-six of 143 (18%) patients survived ≥12 months from relapse or progression, 109 (76%) died within 12 months, and 8 (6%) were alive but had not reached the 12-month landmark. Patients surviving and not surviving 12 months following relapse or progression were comparable for age, gender, international prognostic index at lymphodepletion, performance status, prior stem-cell transplantation (SCT), and first salvage regimens used. Long-term survivors (defined as those surviving 12 months following relapse or progression) had less frequent bridging failure prior to CAR-T therapy (P <.005), as well as less frequent relapse or progression within the first 30 days (P = .027) and more frequent relapse or progression beyond 100 days following CAR-T therapy (P = .011). Long-term survivors received allogeneic SCT for consolidation of treatment responses more frequently (P = .015). Twelve-month OS post-relapse following CAR-T therapy in the 40 patients who proceeded to allogeneic SCT was 34% (range, 19%-39%).

In conclusion, real-world data indicate that long-term survival can be achieved in approximately 20% of patients with R/R LBCL, despite relapse or progression following CAR-T therapy. Favorable predictors of survival included good baseline risk features and a long interval between CAR-T therapy and relapse/progression. Allogeneic SCT successfully consolidated salvage treatment responses in a sizable proportion of patients and may improve outcomes of patients experiencing relapse or progression following CAR-T therapy.


Derigs P, Bethge W, Holtick U, et al. Long-term survivors after failure of CAR-T cell therapy for R/R large B-cell lymphoma: a GLA/DRST study. Presented at: 2022 European Hematology Association Congress, June 9-17, 2022; Vienna, AT. Poster presentation 1448.

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