Diffuse Large B-Cell Lymphoma (DLBCL) Guide

This page is a guide for people newly diagnosed with DLBCL and their families. It covers what the disease is, first-line treatment, pathology report terms, options if it comes back, and when to get help.

Diffuse large B-cell lymphoma is the most common form of non-Hodgkin lymphoma. It starts in B cells, a type of white blood cell. The National Cancer Institute describes it as a lymphoma that "grows quickly in the lymph nodes." It often involves the spleen, liver, bone marrow, or other organs. Many people notice a painless swollen node. Others notice what doctors call B symptoms: fever, drenching night sweats, and weight loss with no clear cause.

DLBCL moves fast. That is frightening to hear. It is also why treatment usually begins within days or weeks, not months. Fast-growing lymphomas are the ones chemotherapy tends to work best against.

DLBCL is aggressive. In a majority of people it is also curable. NCI says most people with localized DLBCL can be cured with chemoimmunotherapy (chemotherapy combined with an antibody drug). About half of people with advanced-stage DLBCL are cured with first-line treatment. The rest either do not respond fully or relapse (the cancer comes back) later. Cure is a word oncologists use with care. They do use it here.

The long-standing standard is R-CHOP. That is rituximab, an antibody against CD20 on B cells, plus cyclophosphamide, doxorubicin, vincristine, and prednisone. The number of cycles depends on stage and risk. NCI describes four to six cycles in many situations.

In April 2023 the FDA approved a second option. It is polatuzumab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone, known as Pola-R-CHP. The approval covers previously untreated DLBCL or high-grade B-cell lymphoma with an International Prognostic Index (IPI) score of 2 or higher. The IPI is a score doctors use to estimate outlook. In the POLARIX trial it improved progression-free survival compared with R-CHOP (hazard ratio 0.73). Progression-free survival is how long people live without the cancer growing. Pola-R-CHP swaps polatuzumab in for vincristine. So it is a change to the same backbone, not a different kind of treatment.

Some people also get treatment aimed at the central nervous system. Some get radiation to a single bulky site. Which approach fits depends on stage, IPI score, and your general health.

Your report may say germinal center B-cell (GCB) type. It may instead say activated B-cell (ABC), also called non-germinal center type. This says which stage of normal B-cell development the lymphoma most resembles. The two types differ in their underlying biology. NCI reports that in the POLARIX trial, Pola-R-CHP helped mainly people with ABC-type tumors. It did not show a benefit for GCB-type tumors, except those with double-hit changes. So ask whether your cell of origin affected the choice of first treatment.

Reports may also mention MYC, BCL2, and BCL6 rearrangements. MYC can be rearranged together with BCL2 or BCL6. That is classified separately as high-grade B-cell lymphoma, sometimes called double-hit. Ask your team whether it changes your treatment plan.

Treatment for relapsed or refractory DLBCL has changed a lot. Refractory means the lymphoma did not respond to treatment. One option is CD19-directed CAR T-cell therapy. Your own T cells are collected and genetically modified to attack the lymphoma. NCI describes trials where CAR T-cell therapy was used as second-line treatment for lymphoma that did not respond to, or came back within 12 months of, first treatment.

Bispecific antibodies are the other major addition. Glofitamab and epcoritamab both received FDA accelerated approval in 2023. That covers relapsed or refractory large B-cell lymphoma after two or more lines of treatment. They bind lymphoma cells and T cells at the same time. They are ready-made, so there is no manufacturing wait. Ask your team where they fit for you.

Both CAR T and bispecifics can cause cytokine release syndrome (a strong, body-wide immune reaction) and side effects on the brain and nerves. That is why they are given at centers set up to monitor for them.

Many people can expect:

• A PET-CT scan before treatment, then scans again midway and at the end
• A port, a small device placed under the skin for giving treatment
• Hair loss, low blood counts, and infection precautions
• Fatigue that builds over cycles

It can help to ask your team about:

• Heart function testing before doxorubicin
• Fertility preservation before the first cycle, if that matters to you. That window is short.

• Call 911 or go to an emergency department if you cannot breathe properly, your face or neck swells, or you become confused, cannot find words, or have a seizure. Confusion and speech trouble matter most in the days after CAR T-cell therapy or a bispecific antibody, when the team is already watching for them. Do not drive yourself.
• Page your lymphoma team the moment it happens, day or night, if your temperature reaches 100.4 °F (38 °C) after a cycle of chemoimmunotherapy. Low white cells are expected after R-CHOP. CDC says to call your doctor immediately at 100.4°F (38°C) or higher during chemotherapy, because an infection can be life-threatening. Do not wait for a second reading. If you cannot get through fast, go to an emergency department and tell them you are on lymphoma treatment. Fever with a racing pulse, low blood pressure or a rash after CAR T or a bispecific can also mean cytokine release syndrome, and is handled the same way.
• Call your care team right away, day or night, if chills or shivering come on, even with a normal temperature, or a mouth sore or line site turns red and painful. Do not wait for a fever to appear (CDC).
• Call your care team within a day or two if a node grows quickly, night sweats soak your bedding again, or you pass much less urine than usual. Report new numbness or weak, heavy legs in the same window, since vincristine affects the nerves.

• FDA: Polatuzumab vedotin-piiq approved for previously untreated DLBCL (April 2023)
• FDA: Accelerated approval of glofitamab-gxbm for relapsed or refractory large B-cell lymphoma
• FDA: Accelerated approval of epcoritamab-bysp for relapsed or refractory DLBCL
• NCI PDQ: Aggressive B-cell non-Hodgkin lymphoma treatment (health professional)
• NCI PDQ: Adult non-Hodgkin lymphoma treatment (patient)
• CDC: Watch out for fever
• NCI: Immunotherapy to treat cancer
• NCI: Infection and neutropenia during cancer treatment
• NCI: T-cell transfer therapy and cytokine release syndrome