A Large Room for Improvement in the Management of Relapsed/Refractory Large B-Cell Lymphoma in Türkiye: Real-World Outcomes in a Setting Without Access to T-Cell Redirecting Therapies.

[OBJECTIVE] Patients with large B-cell lymphoma (LBCL) who are relapsed/refractory (R/R) after frontline therapy have traditionally experienced highly unfavorable outcomes. The development of T-cell redirecting therapies is rapidly changing that outlook, but costs and infrastructural challenges limit access to these innovative therapies. This study was conducted to document the shortcomings of management in the absence of regular access to T-cell redirecting therapies in a contemporary patient population and define the subgroups with the most urgent need for accessing innovative treatments.

[MATERIALS AND METHODS] The second-line management strategies and outcomes of a large real-world LBCL cohort from Türkiye were retrospectively analyzed with the participation of 9 centers from 4 different geographical regions.

[RESULTS] Despite the contemporary nature of the treatment strategies (2012-2024), there was no regular access to novel agents. The median progression-free survival after the first progression (PFS-2) was 6.9 months. Fewer than one-fourth of all patients (24.3%) received transplantation following a response to second-line therapy, constituting the only subgroup to benefit from standard care (2-year PFS-2: 67.8%). The remaining 295 patients (75.7% of the cohort) had median survival of 6.1 months and 2-year PFS-2 of 10.3%. Progression within a year from diagnosis, non-curative intent at the second line of therapy, and failure of curative second-line therapy were key adverse features for a dismal prognosis, with median survival durations of 8.8, 2, and 7.4 months, respectively.

[CONCLUSION] The current therapeutic strategy of intensive chemoimmunotherapy followed by autologous transplantation yields a reasonable chance of survival for only one-fifth of patients. The findings of this study emphasize the urgent need for expanding access to T-cell redirecting approaches in R/R LBCL for early progressors, transplant-ineligible cases, and patients who fail intensive second-line regimens.