Diffuse Large B-Cell Lymphoma (DLBCL)

Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma that develops from B lymphocytes. It is one of the most common types of lymphoma in adults.

DLBCL can occur at any age but is more common in older adults. It usually grows quickly and may develop in lymph nodes or in areas outside the lymphatic system, such as the gastrointestinal tract, central nervous system, bones, or skin.

DLBCL is not a single disease. It can be further classified based on the appearance of the lymphoma cells, immunophenotype, and genetic and molecular features. Understanding these characteristics can help assess risk and guide treatment decisions.

The exact cause of DLBCL is not fully understood. The disease develops through genetic and molecular changes in B lymphocytes that allow abnormal cells to continue growing and multiplying.

Most cases of DLBCL develop on their own, but some may develop when a slower-growing lymphoid cancer transforms into a more aggressive disease. Examples include follicular lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Factors associated with an increased risk of DLBCL may include older age, a weakened immune system, certain autoimmune conditions, and some viral infections. In certain settings, Epstein-Barr virus (EBV) may also be associated with the development of DLBCL.

Having one or more risk factors does not mean that someone will develop DLBCL, and many people diagnosed with DLBCL have no known risk factors.

DLBCL often grows quickly. Common signs and symptoms may include:

• Painless, rapidly growing lymph nodes, often in the neck, armpit, or groin

• Fever

• Night sweats

• Unexplained weight loss

• Ongoing fatigue or weakness

• Loss of appetite

• Abdominal pain or fullness

Unexplained fever, drenching night sweats, and significant weight loss are commonly referred to as B symptoms.

DLBCL can also develop outside the lymph nodes, so symptoms may vary depending on the part of the body involved. For example, lymphoma in the gastrointestinal tract may cause abdominal or digestive symptoms, while a large mass may cause pressure or other symptoms in nearby organs and tissues.

If DLBCL is suspected, a tissue biopsy is usually needed to confirm the diagnosis. Imaging and laboratory tests can then help determine the extent of the disease and its biological characteristics.

Biopsy

A tissue biopsy is essential for diagnosing DLBCL. A sample of an enlarged lymph node or other affected tissue is examined by a pathologist. Immunohistochemistry and other tests are used to determine the type and characteristics of the lymphoma.

When possible, enough tissue is obtained to allow complete pathological and molecular evaluation.

Blood Tests

Blood tests can measure red blood cells, white blood cells, and platelets and assess liver and kidney function. Other laboratory tests may also provide information about disease risk and overall health.

PET/CT

PET/CT is an important imaging test used to stage DLBCL and assess treatment response. It can help show where lymphoma is located throughout the body and evaluate how the disease responds to treatment.

CT and Other Imaging Tests

Depending on the individual situation, CT, MRI, or other imaging tests may be used to provide additional information about the location and extent of the disease.

Bone Marrow Tests

A bone marrow aspiration and/or biopsy may be performed in selected patients to determine whether lymphoma involves the bone marrow.

With the use of PET/CT, a bone marrow biopsy is not routinely required for every person with DLBCL. Whether it is needed depends on the individual situation.

Genetic and Molecular Testing

Additional testing of lymphoma tissue can provide information about its immunophenotypic, chromosomal, genetic, and molecular features.

For example, fluorescence in situ hybridization (FISH) may be used in selected patients to look for rearrangements involving genes such as MYC, BCL2, and BCL6. These findings can help further classify the lymphoma, assess risk, and guide treatment decisions.

Treatment for DLBCL depends on several factors, including the stage of the disease, pathological and molecular features, age, overall health, and previous treatments.

Because DLBCL is an aggressive lymphoma, treatment is usually started soon after the diagnosis and appropriate evaluation. Some patients can achieve long-term remission or cure with first-line treatment. For lymphoma that returns or does not respond adequately to treatment, several additional treatment options are available.

First-Line Treatment

First-line treatment for DLBCL is usually based on immunochemotherapy, which combines a B-cell–targeting monoclonal antibody with chemotherapy.

R-CHOP, which includes rituximab and several chemotherapy medications, is one commonly used first-line regimen. Other treatment approaches may be considered depending on the lymphoma’s pathological and molecular features, stage, and the individual patient.

Radiation Therapy

Radiation therapy may be used in selected patients in addition to systemic treatment, such as in some cases of localized disease, bulky disease, or lymphoma involving certain sites.

Whether radiation therapy is recommended depends on factors such as disease stage, tumor location, treatment response, and the overall treatment plan.

Relapsed or Refractory DLBCL

Some patients may experience a return of the lymphoma after treatment, while others may not respond adequately to initial therapy. This is known as relapsed or refractory DLBCL (R/R DLBCL).

Treatment decisions depend on factors such as how long the lymphoma remained in remission, the characteristics of the disease, age and overall health, and previous treatments.

Several options are now available for relapsed or refractory DLBCL, including different drug combinations, CAR-T cell therapy, and hematopoietic stem cell transplantation.

CAR-T Cell Therapy

CAR-T cell therapy is a type of cellular immunotherapy. A patient’s own T cells are collected and genetically modified in a laboratory so they can recognize a specific target on lymphoma cells. The modified cells are expanded and then infused back into the patient to attack the cancer.

CD19-directed CAR-T cell therapy has become an important treatment option for selected patients with relapsed or refractory large B-cell lymphoma.

Whether CAR-T cell therapy is appropriate depends on factors such as previous treatments, disease status, overall health, and treatment eligibility.

Hematopoietic Stem Cell Transplantation (HSCT)

For some patients with relapsed or refractory DLBCL, autologous hematopoietic stem cell transplantation (auto-HSCT) may still be an important treatment option.

The patient’s own blood-forming stem cells are collected and stored before high-dose chemotherapy is given. The stored stem cells are then returned to the patient to help restore blood cell production.

Whether autologous HSCT is appropriate depends on factors such as response to salvage treatment, timing of relapse, age, overall health, and other available treatment options.

Clinical Trials

Treatment for DLBCL continues to evolve. Clinical trials are studying new medications, cellular therapies, and new combinations or ways of using existing treatments.

For patients with relapsed or refractory disease or those looking for additional treatment options, discussing available clinical trials with the healthcare team may be helpful.