Risk of Relapse in Diffuse Large B-Cell Lymphoma: Understanding Prognosis and Advanced Treatment Strategies

Understanding the Likelihood of Relapse in Diffuse Large B-Cell Lymphoma

Approximately two-thirds of patients diagnosed with diffuse large B-cell lymphoma (DLBCL) may experience disease relapse after initial treatment. This highlights the importance of early and accurate staging, which plays a crucial role in determining long-term outcomes. At the time of diagnosis, it is essential for patients to work closely with their oncologists to undergo comprehensive staging evaluations.

Comprehensive Diagnostic Staging: A Foundation for Effective Treatment

Staging procedures typically include imaging studies such as CT scans of the neck, chest, abdomen, and pelvis, whole-body ultrasound, and bone marrow biopsy. For patients with specific risk factors or neurological symptoms, advanced imaging like contrast-enhanced brain MRI and PET-CT scans are highly recommended. These tools not only help determine the extent of disease spread but also guide personalized treatment planning.

Biomarker Testing After Relapse: Identifying High-Risk Cases

When relapse occurs, further pathological analysis becomes critical. Pathologists often perform additional molecular and genetic testing to assess key biomarkers—such as CD5 expression, EBV status, P53 mutations, C-MYC rearrangements, and overexpression of BCL-2 and BCL-6 proteins. The presence of both C-MYC and BCL-2/BCL-6 abnormalities may indicate "double-expressor" lymphoma, while genetic rearrangements in both C-MYC and BCL-2 or BCL-6 define "double-hit" or "triple-hit" lymphomas.

Why Molecular Subtypes Matter: Impact on Prognosis and Therapy

Patients identified as having double-hit, triple-hit, or double-expressor DLBCL generally face a more aggressive disease course and poorer prognosis. These subtypes are often resistant to standard chemotherapy regimens like R-CHOP, leading to lower response rates and shorter remission durations.

Advanced Therapeutic Approaches for High-Risk DLBCL

For high-risk patients, early intervention with intensified treatment strategies is recommended. This may include adopting dual anti-CD20 immunotherapy regimens—commonly referred to as "double-R" therapy—such as combining rituximab with obinutuzumab or other monoclonal antibodies. In eligible individuals, particularly younger patients with good performance status, incorporating autologous stem cell transplantation (ASCT) earlier in the treatment sequence can improve progression-free survival.

Ongoing clinical trials are also exploring novel agents—including CAR T-cell therapy, antibody-drug conjugates, and targeted inhibitors—for relapsed or refractory DLBCL. These emerging therapies offer renewed hope for patients facing challenging prognoses due to high-risk biological features.