Diffuse Large B-Cell Lymphoma (DLBCL) Guide

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 the so-called 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. Standard first-line chemoimmunotherapy clears the lymphoma in roughly 60% of patients. The rest either do not respond fully or relapse 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. It is usually given every three weeks for six cycles.

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 score of 2 or higher. In the POLARIX trial it improved progression-free survival compared with R-CHOP (hazard ratio 0.73). 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. GCB has historically carried a somewhat better outlook. The two types also differ in their underlying biology. But cell of origin does not currently change standard first-line treatment for most people. It matters more in clinical trials and in relapse.

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. It is often treated more intensively.

Relapsed or refractory DLBCL has changed a lot. One option is CD19-directed CAR T-cell therapy. Your own T cells are collected and genetically modified to attack the lymphoma. It produces responses in a large share of people who have run out of chemotherapy options. For some, those responses last years. CAR T is now used earlier than it once was, sometimes as second-line therapy.

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. They bind lymphoma cells and T cells at the same time. They come off the shelf, with no manufacturing wait. They are options for people who cannot get CAR T, or who have already had it.

Both CAR T and bispecifics can cause cytokine release syndrome and neurologic side effects. That is why they are given at centers set up to monitor for them.

Expect a PET-CT before treatment. Expect scans again mid-way and at the end. Expect port placement, hair loss, low blood counts, and infection precautions. Expect fatigue that builds over cycles. Ask about heart function testing before doxorubicin. Ask about 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.
• 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, and NCI treats fever during treatment as an emergency that needs antibiotics within the hour. 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 the same day if chills or shivering come on without a measured fever, or a mouth sore or line site turns red and painful.
• 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: Immunotherapy to treat cancer
• NCI: Infection and neutropenia during cancer treatment
• NCI: T-cell transfer therapy and cytokine release syndrome