Diffuse Large B-Cell Lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, accounting for approximately 25% to 30% of all cases. This aggressive cancer develops in B-lymphocytes and typically presents as a rapidly growing mass in a lymph node or outside the lymphatic system. Although fast-growing, DLBCL is highly responsive to modern treatment protocols, and a significant proportion of patients can be cured with initial therapy. Treatment is an evolving field that combines established chemotherapy with advanced targeted and cellular therapies.
Standard Initial Treatment Protocols
The initial approach for most newly diagnosed DLBCL patients is the combination chemotherapy regimen known as R-CHOP. The “R” stands for rituximab, a monoclonal antibody that attaches to the CD20 protein on the surface of B-cells. This binding flags the cancerous cells for destruction by the immune system.
The “CHOP” components include three chemotherapy drugs and a steroid: cyclophosphamide, doxorubicin, vincristine, and prednisone. The chemotherapy agents destroy rapidly dividing cells, while prednisone is a corticosteroid that helps kill lymphoma cells and manages side effects. R-CHOP is administered in cycles, typically every 21 days, with six cycles common for advanced-stage disease.
For certain high-risk subtypes of DLBCL, a modified regimen called R-EPOCH may be used, involving continuous, dose-adjusted infusions of chemotherapy drugs. R-CHOP remains the standard of care that improved patient outcomes following the addition of rituximab. A newer regimen, Pola-R-CHP, replaces vincristine with the antibody-drug conjugate polatuzumab vedotin. Pola-R-CHP is now used for previously untreated DLBCL, showing improved progression-free survival compared to R-CHOP.
Managing Relapsed or Refractory Disease
If DLBCL returns after remission (relapsed) or does not fully respond to R-CHOP (refractory), the strategy shifts to a second-line, or “salvage,” approach. Salvage therapy aims to reduce the cancer burden enough for high-dose treatment. These regimens are often platinum-based, including combinations like R-ICE or R-DHAP.
These intense combinations are given for two to three cycles to determine if the cancer is “chemosensitive.” If a patient achieves a partial or complete response and is healthy enough, the next step is high-dose chemotherapy followed by an autologous stem cell transplant (ASCT). In ASCT, the patient’s own healthy blood stem cells are collected and stored before a very high dose of chemotherapy eliminates remaining cancer cells.
The stored stem cells are then reinfused to “rescue” the bone marrow, allowing the body to produce new, healthy blood cells. ASCT has been the standard curative approach for eligible patients with chemosensitive relapsed DLBCL. However, this complex procedure is highly intensive and not suitable for all patients due to age or other health conditions.
Advanced Targeted and Immunotherapies
For patients whose DLBCL is refractory to initial treatment and salvage chemotherapy, or who relapse soon after first-line treatment, the landscape includes advanced cellular and targeted therapies. Chimeric Antigen Receptor (CAR) T-cell therapy involves genetically re-engineering a patient’s own T-cells to recognize and kill lymphoma cells. The T-cells are collected, modified in a lab to target a protein like CD19, and then infused back into the patient.
CAR T-cell therapy has demonstrated durable remission in patients who previously had limited options. This treatment is approved for use in the second-line setting for patients whose disease is refractory or relapses within a year of frontline therapy. Bispecific antibodies are a newer class of immunotherapy, primarily for later lines of treatment.
These antibodies have two “arms”: one binds to a cancer cell marker (e.g., CD20), and the other binds to a T-cell marker (e.g., CD3). By bridging the T-cell and the cancer cell, these antibodies redirect the immune system to attack the lymphoma. Polatuzumab vedotin is an antibody-drug conjugate (ADC) that links an anti-CD79b antibody to a potent chemotherapy drug. This design allows for targeted delivery of chemotherapy directly to the lymphoma cells, minimizing damage to healthy tissue.
Life After Treatment: Monitoring and Follow-Up Care
Once a patient achieves a complete response to DLBCL therapy, follow-up care monitors for recurrence and manages long-term side effects. Most relapses occur within the first two years, so patients are seen frequently during this period. Visits include a physical examination, symptom review, and blood tests, such as a complete blood count and lactate dehydrogenase (LDH) levels.
The use of routine surveillance imaging, such as PET or CT scans, is debated, as most relapses are detected when a patient reports new symptoms. However, many centers continue to utilize scans, especially in the first two years. As the risk of recurrence drops, follow-up shifts to monitoring for “late effects” of the intensive treatments.
A significant concern is the potential for cardiac issues due to doxorubicin, a component of R-CHOP. Patients may also face an increased risk of secondary cancers or long-term nerve damage (neuropathy) from vincristine. Survivorship clinics educate patients about these risks, manage late-onset complications, and promote a healthy lifestyle after treatment.