Survival Improvement of DLBCL Patients Treated with Third Line and Beyond in the Recent Era in the Czech Republic

The prognosis of patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) has been considered to be poor. Although innovative agents such as CAR-T, bispecific antibodies, and antibody-drug conjugates have transformed the therapeutic landscape, their impact on survival at population level has not been comprehensively evaluated. We therefore aimed to assess temporal changes in overall survival (OS) among patients receiving third-line (L3) therapy in recent years. We analyzed 312 consecutive L3-treated r/r DLBCL patients from the prospective NiHiL project (NCT03199066) of the Czech Lymphoma Study Group. Patients were divided in two treatment eras based on CAR-T availability: Era 1 (2018-2020; n=134) and Era 2 (2021-2023; n=178). The primary endpoint was OS; secondary endpoints were event-free survival (EFS), response rates, and treatment patterns. OS significantly improved in Era 2 compared with Era 1 (HR=0.70, P=0.01), with 2-year OS of 43% versus 29%, respectively. Two-year EFS increased from 13% to 24% (HR=0.70; P=0.01). Complete remission rates improved from 18% to 30% (P=0.02). Treatment patterns shifted markedly, with increased use of CAR-T therapy (6% to 32%) and other novel agents (13% to 22%; P<0.01). More pronounced survival benefit was observed in CAR-T-eligible cohort (n=202). This real-world study is the first to demonstrate that the incorporation of new therapies has led to significant and clinically meaningful OS improvement in the general r/r DLBCL L3-treated population. These findings underscore the importance of continued integration and sequencing of innovative treatments into clinical practice and inclusion of patients in clinical trials.