Advances in diffuse large B-cell lymphoma treatment may improve outcomes for people who are living with this type of cancer.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma. Non-Hodgkin’s lymphoma develops in white blood cells called lymphocytes. B cells are a specific type of white blood cell.

In DLBCL, the B cells start to grow in an abnormal way. Typically, B cells help fight infections. But in someone with DLBCL, the B cells are larger than usual and don’t work like healthy B cells. These cancerous cells grow quickly and take over, blocking any healthy B cells.

Chemotherapy is generally the first treatment for DLBCL, but it isn’t right for everyone for many reasons. Plus, not everyone with DLBCL responds to chemotherapy.

Thanks to advances in cancer research, healthcare teams have developed new approaches to treating DLBCL.

Read on to learn more about the current and potential future treatments for DLBCL.

DLBCL is a fast-growing type of cancer. In some people, first-line treatment using chemotherapy is effective. But in many cases, a different approach is necessary. In up to 40% of people with DLBCL, the cancer does not fully respond to first-line treatment or comes back after treatment.

There have been advances in treatment for DLBCL and other types of cancer, and there are now options for people whose cancer doesn’t respond to first-line treatment. Past and present clinical trials have led to other effective treatments for DLBCL.


In the early days of treating DLBCL, people were treated with a variety of chemotherapy regimens. The use of a specific combination of chemotherapy medications known as CHOP started in the 1970s. By the early 1990s, CHOP showed the best outcomes and became the go-to treatment for many types of B-cell lymphomas.

CHOP is a combination of three chemotherapy drugs and a steroid (prednisone). These medications work together to destroy cancer cells and stop or slow the growth of new ones.

CHOP is named for the medications that are used in the treatment regimen:

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


Building on the good outcomes of the CHOP regimen, researchers explored how to make it even better.

This led to the addition of a medication called rituximab, which is a type of monoclonal antibody. It acts similarly to your body’s antibodies to destroy harmful invaders. It attaches to the surface of B cells and then sends signals to your immune system to destroy them.

The addition of rituximab was shown to improve outcomes for people with DLBCL, specifically those with a particular marker (CD20). This new combination, known as R-CHOP, increased the cure rate of DLBCL by 10–15%.

R-CHOP stands for:

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

R-CHOP is now considered first-line therapy for DLBCL.

Salvage chemotherapy with autologous stem cell transplant

“Salvage chemotherapy” is the term for a second, different mix of chemotherapy medications that may be used if R-CHOP doesn’t work. But there’s not one standard second combination. Your doctor will discuss other chemotherapy medications you can try if your DLBCL does not respond to R-CHOP.

If your lymphoma responds to this second round of chemotherapy, you may be a candidate for autologous stem cell transplantation (ASCT).

ASCT is a complicated procedure and is not right for everyone. It involves using your own healthy stem cells to reestablish normal blood cell production in your bone marrow. Stem cells are made in the marrow and mature into different blood cells. But not everyone has enough stem cells available to do ASCT.

Generally, if the second type of chemotherapy does not work, a stem cell transplant is not a good option.

Targeted therapies

Targeted therapies are a class of medications that recognize and target specific proteins found in or on cancer cells. Rather than targeting all cells, they stop or slow the growth of cancer cells only.

Targeted therapies often use your own immune system to attack cancer cells.

You might receive a targeted therapy medication along with other treatments, such as chemotherapy.

Monoclonal antibodies are a type of targeted therapy. Some monoclonal antibodies used in treating DLBCL are:

  • rituximab (Rituxan), which is used as part of the R-CHOP regimen
  • polatuzumab vedotin (Polivy)
  • tafasitamab (Monjuvi)
  • epcoritamab (Epkinly)
  • glofitamab (Columvi)

Nuclear export inhibitors, such as selinexor (Xprovio), are another class of targeted therapy that is sometimes used for relapsed or refractory DLBCL. But there are more effective options out there.

Polatuzumab vedotin (Polivy) shows promise in a few ways. Some people may take polatuzumab along with bendamustine (a chemotherapy medication) and rituximab if their DLBCL doesn’t respond to R-CHOP.

Other research suggests that polatuzumab vedotin could become a part of first-line therapy. Early clinical trial results suggest that replacing the vincristine sulfate (Oncovin) in R-CHOP with polatuzumab vedotin may increase survival. But more research is needed.

A combination of medications, tafasitamab (Monjuvi) and lenalidomide (Revlimid), was approved in 2020 after clinical trials showed that it was effective in some people.

It’s recommended for people whose DLBCL does not respond to R-CHOP and who are not good candidates for ASCT. Tafasitamab is a monoclonal antibody, and lenalidomide is a chemotherapy medication.

A doctor may also recommend mosunetuzumab if you cannot tolerate chemotherapy. A study from 2020 included people who weren’t able to tolerate the R-CHOP regimen because of their health at the time of diagnosis. The results showed that people in the study had an overall response rate of 58% to the mosunetuzumab.

CAR T-cell therapy

Chimeric antigen receptor (CAR) T-cell therapy is a newer treatment regimen for DLBCL. It may be an option for you if R-CHOP and one other chemotherapy regimen do not work.

CAR T-cell therapy is a type of immunotherapy. Scientists have figured out how to use a person’s own T cells (another part of the immune system) to target and destroy cancerous B cells.

You can ask your healthcare team about any ongoing clinical trials that you might be able to participate in. Clinical trials are helpful for advancing treatments for DLBCL. They may also offer a chance to try a new therapy that is not yet widely available.

Some clinical trials are currently enrolling people with DLBCL.

Research has already shown good outcomes with the combination of tafasitamab and lenalidomide in people whose DLBCL does not respond to R-CHOP. A clinical trial is exploring whether adding another medication — either tazemetostat or zanubrutinib — will have greater benefit. Both tazemetostat and zanubrutinib are targeted therapy medications.

R-CHOP has been the first-line treatment for many years. Researchers want to explore whether a combination of targeted therapies — venetoclax, ibrutinib, prednisone, obinutuzumab, and revlimid (ViPOR) — might be effective for people whose DLBCL has not responded to R-CHOP.

It would be helpful to have a second standard treatment regimen in case R-CHOP does not work.

DLBCL is a fast-growing type of cancer. It’s best to start treatment soon after you receive a diagnosis. Many factors affect survival with DLBCL, including your age, the stage of your DLBCL, and other health conditions you have.

The overall 5-year relative survival rate for DLBCL is 65%. That means, compared to someone without cancer, a person with DLBCL is 65% as likely to be alive 5 years after diagnosis.

Diffuse large B-cell lymphoma (DLBCL) is a type of cancer that causes B cells to grow abnormally large and quickly. R-CHOP is typically the first treatment for DLBCL. But chemotherapy is not a good treatment option for everyone, and about 40% of people with DLBCL do not have a complete response to R-CHOP.

There are also several newer treatments for DLBCL, including many targeted therapy options. Your doctor will discuss your options with you so you understand your next steps.