Stage 4 diffuse large B-cell lymphoma (DLBCL) is a rapidly growing lymphoma affecting at least one other organ outside the lymphatic system.

Cancer is the unusual growth and spread of cells within the body. When cancer originates in the lymph nodes of the lymphatic system, it is known as lymphoma. Many types of lymphoma exist, defined by their origin, location in the body, and cell characteristics.

Diffuse large B-cell lymphoma is the most common type of lymphoma. It makes up approximately 25% of all non-Hodgkin’s lymphomas, which are cancers that lack defining cells called Hodgkin cells and Reed-Strenberg cells.

While it can feel overwhelming to receive a diagnosis of DLBCL, learning about this condition can help a person navigate the treatment process.

DLBCL is a large B-cell lymphoma with a diffuse pattern, meaning that the cancer cells are spread within the lymph node and do not appear in clusters. It is a type of non-Hodgkin’s lymphoma originating from B cells, which are white blood cells responsible for creating antibodies.

At stage 4, DLBCL has spread to at least one other location in the body outside of the lymphatic system, making the cancer metastatic or widespread.

The term “large B cell” is used because cancerous cells in DLBCL have an unusually large appearance when seen under a microscope.

Types of DLBCL

Several subtypes of DLBCL exist. Doctors distinguish them by unique characteristics, such as their cell of origin (COO), location in the lymphatic system, and genetic components.

Types of DLBCL by COO include:

  • Germinal center B-cell-like (GCB): Originates in B cells undergoing specialization in the germinal center of the lymph node.
  • Activated B-cell-like (ABC): Originates in B cells within the germinal center that have already been activated by antigens but are not fully matured.

Examples of genetic subtypes of DLBCL include:

  • Double-hit lymphoma (DHL): DLBCL linked to genetic variants of the MYC gene and the BCL2 or BCL6 gene.
  • Triple-hit lymphoma (THL): DLBCL linked to genetic variants of the MYC, BCL2, and BCL6 genes.

Examples of DLBCL subtypes classified by location in the body include:

  • Primary central nervous system (CNS) DLBCL: Located in the brain and spinal cord.
  • Primary cutaneous BLBCL, leg type: Affecting the skin, primarily on the legs.

What is CNS prophylaxis in DLBCL?

When doctors consider a person at high risk for the spread of cancer into the CNS, they may recommend CNS prophylaxis. This preventive treatment is a type of chemotherapy doctors administer to prevent DLBCL from affecting the brain and spinal cord.

Prophylaxis treatment may also be necessary for people with DLBCL at high risk for cancer’s return after remission with standard therapies.

Oncologists, or cancer specialists, provide CNS prophylaxis by injecting chemotherapy agents directly into the spinal cord fluid. This procedure, known as intrathecal chemotherapy, allows anticancer drugs direct access to the CNS, which the blood-brain barrier might otherwise restrict.

CNS prophylaxis may also involve intravenous (IV) infusions of high dose methotrexate, a chemotherapy agent that can effectively cross the blood-brain barrier.

The American Cancer Society lists the 5-year relative survival rate for DLBCL, which doctors have diagnosed as distant DLBCL, at 58%. The Surveillance, Epidemiology, and End Results (SEER) database defines distant DLBCL as cancer that has spread to distant parts of the body, such as the lungs, liver, or bone marrow.

This does not mean 58% of people with distant DLCBL survive for 5 years. It means a person with a diagnosis of distant DLCBL is 58% as likely as someone without cancer to live for another 5 years after diagnosis.

How long can you live with DLCBL?

Doctors cannot accurately predict a person’s life span after a stage 4 DLCBL diagnosis. Survivorship depends on multiple factors, including overall health, co-existing conditions, and the cancer’s location.

In general, DLCBL is highly treatable and curative for as many as 50% of people who achieve complete remission after first-line therapies.

When cancer is advanced, as in stage 4 DLCBL, survival rates decrease due to the complexity of cancer outside of the lymphatic system, but remission is still possible.

The National Cancer Institute notes that around 6% of people with stage 4 DLCBL achieve or exceed the 5-year survival mark.

Is DLCBL always terminal?

DLCBL is not always terminal. Depending on its stage, it is considered potentially curable and highly treatable. Even at stage 4, remission — a decrease or absence of clinical cancer signs — is possible with treatment.

Oncologists treat stage 4 DLCBL with chemotherapy. First-line protocols include R-CHOP and pola-R-CHP, which refer to the combination of drugs used in the treatment.

CHOP regimens for stage 4 DLCBL consist of monoclonal antibodies (polatuzumab vedotin and rituximab) combined with chemotherapy agents such as cyclophosphamide, doxorubicin, and prednisone.

R-CHOP stands for:

  • R: rituximab
  • C: cyclophosphamide
  • H: doxorubicin hydrochloride (Hydroxydaunomycin)
  • O: vincristine sulfate (Oncovin)
  • P: prednisone

Pola-R-CHP stands for:

  • Pola: polatuzumab vedotin
  • R: rituximab
  • C: cyclophosphamide
  • H: doxorubicin hydrochloride (Hydroxydaunomycin)
  • P: prednisone

After 3 or more cycles of treatment, doctors re-evaluate DLCBL with diagnostic imaging to check whether the cancer is responding to therapy.

Other medication combinations and prophylaxis therapy may be necessary based on a person’s diagnosis and individual needs.

Stem cell transplants may help restore the body’s population of B cells in younger people who respond well to chemotherapy.

Clinical trials are research studies that assess the safety and effectiveness of emerging therapies.

Participating in a clinical trial has several benefits. It can provide access to otherwise unavailable treatments that might make a difference in stage 4 DLBCL outcomes. People participating in these studies also gain the support of a highly skilled team of researchers and medical professionals, often at a lower cost than traditional cancer care.

People can explore clinical trials for DLBCL at ClinicalTrials.gov. Some studies currently seeking participants include:

Clinical trials are not appropriate for everyone. People interested in participating should discuss the option with an oncologist first.

Even at stage 4, DLBCL is treatable, and remission is possible. A person’s outlook will depend on many factors, including response to treatment and their individual International Prognostic Index (IPI) score.

IPI score suggests a good or less favorable outlook based on factors such as:

  • age
  • lymphoma stage
  • metastasis
  • overall daily function
  • blood level of lactate dehydrogenase (LDH), which increases as lymphoma grows and spreads

Stage 4 DLBCL is a type of lymphoma that has spread to at least one site outside the lymphatic system.

Although doctors consider it an advanced-stage cancer, it is treatable, and remission is possible for some people.