Frontline Sequencing and Impact on Relapse Options in DLBCL

Dr. Johnson addresses whether using CD19-directed agents in the frontline compromises subsequent relapse options. His general philosophy is to use the most effective available therapy at each decision point without excessive concern about downstream sequencing, though he acknowledges prospective data would be helpful. He notes reassuring real-world data presented at EHA 2026 showing relatively encouraging anti-CD19 CAR-T outcomes in patients previously exposed to tafasitamab, though this remains retrospective data with inherent limitations.

Dr. Lunning raises concern about the current disconnect between frontline treating teams and CAR-T manufacturing centers, noting that manufacturers don't consistently receive information about prior novel agents, including tafasitamab, polatuzumab vedotin, or clinical trial drugs, before apheresis, potentially creating unrecognized manufacturing challenges. He calls for standardized communication protocols.

The panel discusses the second-line landscape's shift toward earlier identification of primary refractory or early-relapsing patients using post-treatment ctDNA surveillance. Detecting low-volume relapse before symptomatic progression may allow patients to reach anti-CD19 CAR-T with the least disease burden and the least T-cell perturbation from salvage therapies, both of which are known predictors of CAR-T success. Dr. Lunning notes that the timing and choice of bridging therapy before apheresis have become increasingly sophisticated considerations, given that bendamustine in particular can significantly compromise T-cell collection and CAR-T product quality.