This protocol addresses diffuse large B-cell lymphoma (DLBCL) at the third treatment line — the step indicated when second-line therapy has not achieved the response required to proceed, or when the disease has relapsed following second-line interventions.
Second-line treatment for DLBCL encompasses CAR T-cell therapy (axi-cel or liso-cel) for primary refractory or early-relapsing disease, and platinum-based salvage chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) for disease relapsing more than one year after initial treatment. Progression to the third line is indicated when at least a partial response to salvage therapy is not demonstrated — the threshold required before ASCT can proceed — or when disease progresses after these second-line approaches including after CAR T-cell therapy or ASCT.
For patients who have received at least two prior lines of therapy and have not yet received CAR T-cell therapy, CAR T-cell therapy is the treatment of choice. For those ineligible for this approach or whose disease has relapsed after it, several targeted antibody-based and bispecific antibody regimens are available. The complete eligibility criteria, regimen selection, and sequencing algorithm are in the full protocol.
DOI: 10.1038/s41408-026-01458-2