Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma and the Real-World Data Perspective

Abstrakt

Management of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) has undergone significant transformation in recent years. Second-line therapy has shifted from conventional salvage regimens toward immunotherapy-based approaches. CAR T-cell therapy is now the preferred option for patients with early relapse or primary refractory disease, while salvage chemoimmunotherapy followed by autologous stem cell transplantation consolidation remains reserved for younger, fit individuals with late relapses. Bispecific antibodies (BiAbs) combined with chemotherapy (i.e., glofitamab plus GemOx) could be effective alternatives for transplant-ineligible patients. Additional novel options include Pola-BR and tafasitamab-lenalidomide, particularly for elderly or frail individuals.

In third-line and later settings, treatment is increasingly individualized. CAR T-cell therapy remains the preferred modality if not previously administered; otherwise, BiAbs (glofitamab, epcoritamab, odronextamab), antibody-drug conjugates (loncastuximab tesirine, brentuximab vedotin), and lenalidomide-based regimens are considered. Real-world data from the NiHiL registry support the clinical utility of these novel agents and demonstrate improved survival outcomes following their integration into routine clinical practice.