Patients with diffuse large B-cell lymphoma (DLBCL) who relapse after initial treatment, or whose disease is refractory to first-line therapy, require a distinct second-line strategy. The approach is not uniform — it depends critically on when the disease returns or fails to respond.

Clinical Scenario

This protocol covers DLBCL patients with primary refractory disease or relapse following initial treatment. Two distinct populations are addressed: those with early treatment failure or progression, and those with a later relapse — each carrying a different prognosis and a different therapeutic path.

Treatment Approach — Partial Overview

Second-line management is stratified by the timing of relapse. For patients with primary refractory disease or progression within approximately one year of diagnosis, a CD19-directed cellular immunotherapy is the preferred approach, and bridging therapy is commonly given beforehand to maintain disease control. For patients who relapse later, the strategy shifts to a platinum-based salvage chemoimmunotherapy combination, with the goal of achieving sufficient disease response before proceeding to a high-dose consolidative treatment. The complete regimen selection, sequencing criteria, and bridging options are detailed in the full protocol.

Key Clinical Goal

Demonstrating at least a partial response to salvage therapy is required before a patient can proceed to consolidative high-dose treatment. Chemosensitivity is an established prognostic requirement at this stage.

References

DOI: 10.1038/s41408-026-01458-2

For patients with primary refractory disease or those whose disease progresses within 1 year of diagnosis, the treatment of choice is to utilize CAR T-cell therapy.
Axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) are both approved treatments for these patients based on the ZUMA-7 and TRANSFORM clinical trials, respectively.
For these patients, bridging therapy is commonly given to maintain disease control.
Bridging therapy may take the form of localized radiation therapy or combination chemoimmunotherapy utilizing antibody-drug conjugates and chemotherapy.
These patients with a later relapse constitute a lower risk population, and high-dose therapy followed by ASCT remains the standard of care for this group.
Lack of chemosensitivity is an established adverse prognostic factor for patients with DLBCL and so patients need to demonstrate at least a partial response to salvage therapy to receive an ASCT.

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What Is the Treatment of Diffuse Large B-Cell Lymphoma After Relapse or Refractory Disease?

References