Germinal Center B-cell-like Diffuse Large B-cell Lymphoma (GCB DLBCL) is a specific subtype of non-Hodgkin lymphoma. This fast-growing cancer develops in B-lymphocytes, a type of white blood cell. DLBCL is the most common form of non-Hodgkin lymphoma, and GCB DLBCL accounts for approximately 50-60% of all DLBCL cases.
Characteristics of GCB DLBCL
Diffuse Large B-cell Lymphoma is a heterogeneous group with varying molecular characteristics and clinical behaviors. GCB DLBCL is one of the main molecular subtypes, distinguished by its gene expression profile, which closely resembles normal germinal center B-cells. These cells normally reside in the germinal centers of lymphoid tissues, where B-cells mature and diversify. The GCB subtype expresses specific genes such as BCL6, CD10, and LMO2.
Patients with GCB DLBCL may experience common signs and symptoms. These can include rapidly growing lymph nodes in the neck, armpit, or groin. Some individuals may also develop “B symptoms,” including unexplained fevers, drenching night sweats, and significant unintentional weight loss. Molecular subtyping, particularly differentiating GCB DLBCL from Activated B-cell-like (ABC) DLBCL, is important due to different prognoses and treatment responses.
Molecular classification, often through gene expression profiling (GEP), helps identify the cell of origin. Immunohistochemistry (IHC) using markers such as CD10, BCL6, and MUM1 can also infer the GCB subtype, with the Hans algorithm being a common method. GCB DLBCL is associated with a better response to standard treatments and more favorable overall survival compared to ABC DLBCL.
Diagnosing GCB DLBCL
The definitive diagnosis of GCB DLBCL begins with a biopsy, most commonly an excisional lymph node biopsy. Pathology examination involves assessing cell morphology and performing immunohistochemistry (IHC). GCB DLBCL is often CD10 positive, BCL6 positive, and MUM1 negative, though other combinations can also indicate the GCB subtype.
Molecular testing, particularly gene expression profiling (GEP), is the standard for accurately subtyping DLBCL into GCB and ABC forms. While GEP provides precise classification by analyzing gene activity, IHC methods like the Hans algorithm offer a practical alternative with approximately 80% consistency with GEP results. Staging procedures determine the extent of the disease. These include PET-CT scans, which identify areas of increased metabolic activity, and sometimes a bone marrow biopsy to check for lymphoma involvement.
Treatment Approaches for GCB DLBCL
The standard first-line treatment for GCB DLBCL is the combination chemotherapy regimen known as R-CHOP. This regimen consists of Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), and Prednisone. Rituximab is a monoclonal antibody that targets the CD20 protein on B-cells, helping the immune system destroy lymphoma cells. The other four drugs are chemotherapy agents that interfere with cancer cell growth and division.
R-CHOP is effective for GCB DLBCL, often leading to better outcomes than in ABC DLBCL. This regimen has been a primary first-line therapy for DLBCL for over 20 years, achieving long-term disease control in many patients. Approximately 30-40% of patients may not respond to initial treatment or experience a relapse. For these cases, other treatment approaches are considered.
High-dose chemotherapy followed by autologous stem cell transplant may be an option for eligible patients, where their own healthy stem cells are reinfused after intensive treatment. Chimeric Antigen Receptor (CAR) T-cell therapy is another advanced treatment, genetically modifying a patient’s T-cells to recognize and attack lymphoma cells. Newer targeted therapies, such as Polatuzumab vedotin and Tafasitamab (often combined with lenalidomide), are also approved for relapsed or refractory DLBCL.
Outlook and Management
GCB DLBCL generally has a more favorable outlook compared to other DLBCL subtypes, particularly the ABC type, when treated with R-CHOP therapy. The overall response rate to R-CHOP in GCB DLBCL patients is around 80-90%, with a 5-year overall survival rate of approximately 60-70%. Cure rates of about 70-80% are indicated with R-CHOP. For patients who remain disease-free for two years after frontline therapy, survival rates can be similar to the general population.
After completing treatment, regular post-treatment follow-up monitors for remission and detects potential recurrence. This involves scheduled check-ups, imaging scans like PET-CT, and blood tests. Supportive care and managing potential long-term side effects are also important aspects of ongoing management.