Diffuse Large B-Cell Lymphoma (DLBCL) is a rapidly growing form of non-Hodgkin lymphoma, originating from B-lymphocytes. While initial treatments can lead to remission, some patients may experience a relapse, meaning the cancer returns after a period of being undetectable.
Relapse Rates and Risk Factors
Approximately 30% to 40% of individuals diagnosed with Diffuse Large B-Cell Lymphoma (DLBCL) may experience a relapse following standard first-line therapy, such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). An individual’s specific risk can vary considerably based on several factors.
Relapsed DLBCL occurs when the cancer reappears after a period of complete remission. In contrast, refractory DLBCL describes cancer that either does not respond to initial treatment or progresses shortly after treatment completion. About 20% of patients may have primary refractory disease, meaning their DLBCL becomes resistant to R-CHOP or progresses during or immediately after treatment.
The International Prognostic Index (IPI) is a widely used tool to assess the risk of relapse and predict outcomes in DLBCL patients. This scoring system considers five clinical factors:
Age over 60 years
Ann Arbor stage III or IV disease
An elevated serum lactate dehydrogenase (LDH) level
A performance status score of two or higher
The presence of more than one extranodal site of disease
A higher IPI score indicates a greater risk of the disease returning.
Molecular characteristics of the lymphoma cells also play a role in determining relapse risk. DLBCL can be broadly categorized into molecular subtypes based on their “Cell-of-Origin” (COO), specifically Germinal Center B-cell-like (GCB) and Activated B-cell-like (ABC). Patients with the ABC subtype have historically faced less favorable outcomes when treated with standard immunochemotherapy.
A more aggressive form of DLBCL, known as High-Grade B-cell Lymphoma (HGBL), carries a significantly higher risk of early relapse. This classification includes lymphomas with specific genetic rearrangements, often involving the MYC gene in combination with BCL2 and/or BCL6 genes. These are sometimes referred to as “double-hit” (MYC and BCL2 or BCL6 rearrangements) or “triple-hit” (MYC, BCL2, and BCL6 rearrangements) lymphomas.
The Timeline for Relapse and Monitoring
The majority of DLBCL relapses typically occur within the first two years following the completion of primary therapy. Relapses occurring after five years are uncommon. This two-year window is considered the period of highest risk for the cancer to return.
Following the completion of initial treatment and achievement of remission, patients typically undergo a structured follow-up care schedule. This often involves regular physical examinations, blood tests, and consultations with the oncology team. Blood tests, including complete blood counts (CBC) and lactate dehydrogenase (LDH) levels, offer insights into a patient’s general health and potential disease activity.
Imaging studies, including PET-CT (Positron Emission Tomography-Computed Tomography) or CT scans, are commonly used in monitoring. Routine, scheduled imaging for patients who are asymptomatic and have no concerning blood work is becoming less common. Scans are generally performed if a patient develops new symptoms or if blood test results suggest a potential issue.
Patients should promptly report any new or persistent symptoms. Symptoms such as new or growing lumps, unexplained fevers, drenching night sweats, or unintentional weight loss should be reported to the medical team.
Treatment Pathways After Relapse
When Diffuse Large B-Cell Lymphoma (DLBCL) returns after a period of remission or proves refractory to initial therapy, a biopsy is almost always necessary. This step confirms the relapse and allows for a re-evaluation of the lymphoma’s characteristics, which guides subsequent treatment decisions. The re-biopsy can also identify any changes in the lymphoma’s molecular profile.
Autologous Stem Cell Transplantation (ASCT)
For eligible patients whose lymphoma remains sensitive to chemotherapy, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard approach. This process involves administering strong chemotherapy to eliminate lymphoma cells, followed by the reinfusion of the patient’s own healthy stem cells, which were collected before the chemotherapy. These reinfused stem cells then help to rebuild the bone marrow, which is severely impacted by the high-dose chemotherapy.
CAR T-cell Therapy
Chimeric Antigen Receptor (CAR) T-cell therapy represents a significant advance for patients with relapsed or refractory DLBCL, particularly for those who are not candidates for ASCT or who relapse after it. In this therapy, a patient’s own T-cells are collected and genetically modified in a laboratory to express a chimeric antigen receptor that specifically targets lymphoma cells. These engineered T-cells are then expanded in number and reinfused into the patient’s bloodstream to seek out and destroy cancer cells.
Other Therapeutic Options
Beyond ASCT and CAR T-cell therapy, other therapeutic options are available for relapsed or refractory DLBCL. These include targeted therapies, antibody-drug conjugates, and bispecific antibodies. Clinical trials offer access to the newest treatments and are an important consideration for patients exploring additional options.