Refractory and relapsed DLBCL both present several treatment challenges, but available and upcoming options may help improve outcomes.

Diffuse large B-cell lymphoma (DLBCL) is a subtype of non-Hodgkin’s lymphoma. Though many people will respond to first-line treatment options, many will experience refractory or relapsed DLBCL.

When this happens, oncologists need to try different methods to gain a response to treatment or remission.

This article reviews some of the current treatments alongside some potential options undergoing clinical trials for people living with refractory or relapsed DLBCL.

DLBCL is the most common type of non-Hodgkin lymphoma in the United States. About 40% of people will not respond to first-line treatment (refractory) or experience a recurrence (relapse).

Those living with refractory or relapsed DLBCL have a less favorable overall survival rate. However, this is based on limited data on specific groups of people, meaning some groups do have an unfavorable survival rate, but others do not.

Newer treatment options, as well as those currently in clinical studies, may help improve overall survival for those with refractory or relapsed DLBCL.

All treatment options may cause different side effects. A person can discuss possible side effects with an oncologist to determine if the benefit outweighs the risk of potential side effects.


CHOP stands for:

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

CHOP is a combination of three chemotherapy drugs and a hormonal steroid (prednisone). Each medication targets the cancer cells in a slightly different way, which can increase the overall effectiveness of the treatment.

A person receives the chemotherapy medications via an intravenous drip, often thin silicone tubing placed into a large vein in the chest. They will take prednisone as an oral tablet.

The CHOP combination started in the 1970s, and researchers updated it in the early 2000s to create the rituximab R-CHOP combination treatment.


R-CHOP stands for:

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

R-CHOP keeps the basic CHOP formula but has the addition of a monoclonal antibody drug called rituximab. This helps provide targeted treatment to the cancer cells with a particular marker (CD20).

Several studies found that adding rituximab to CHOP improved outcomes for people living with DLBCL compared to CHOP alone.

Targeted therapies

Targeted therapies are a specific, specialized type of cancer treatment. They target particular proteins and structures on cancer cells responsible for their growth, division, and spreading.

There are two types available, including small molecule drugs and monoclonal antibodies. Small molecule drugs can easily enter cells and are generally easier to produce. Monoclonal antibodies require labs to grow proteins.

Both treatments find and interfere only with cancer cells, which eliminates some of the side effects experienced with chemotherapy. However, they can be more expensive and challenging to produce, and cancer can develop resistance to them.

A 2020 meta-analysis found that targeted therapies increase overall survival rates and response to treatment in people living with DLBCL. However, rituximab can increase the risk of infections.

CAR T-cell therapy

CAR T-cell therapy is a type of targeted immunotherapy used to treat relapsed or refractory DLBCL. CAR T-cell therapy involves harvesting T cells, which are part of the immune system, through a blood draw and altering them by adding certain genes in a lab to target cancer cells.

Once altered, the medical professional places the T cells back to the person to help combat their cancer.

Evidence suggests that CAR T-cell therapy may be effective in treating DLBCL and has become the standard for treatment for new cases of relapsed and refractory DLBCL.

Immunomodulatory drugs

Immunomodulatory drugs modify how the immune system responds to different cells. In the case of DLBCL, it involves using the immune system to find and attack cancer cells to prevent their growth and spread.

Current studies and clinical trials indicate that certain combinations of immunomodulatory drugs may help with DLBCL as a potentially chemotherapy-free treatment option.

Continuing studies will help determine its overall effectiveness and safety in treating relapsing or refractory DLBCL.

Clinical trials are studies that examine new or novel drugs, therapies, or combinations of existing medications. They comprise several stages that involve increasing the number of people to test the effectiveness and safety across wider ranges of the population.

Several clinical trials are underway for new treatments for DLBCL.

Some trials are examining the effectiveness of CAR T-cell therapies. Results from recent studies suggest a 4-year survival rate of 55% may be possible with the therapy.

Another clinical trial is underway examining how a combination of medications — venetoclax, ibrutinib, prednisone, obinutuzumab, and revlimid in combination with polatuzumab (ViPOR-P) — may affect DLBCL. The trial is not yet complete.

The overall outlook for people living with refractory or relapsed DLBCL is unfavorable. The overall response rate to treatment is about 26%, and complete remission occurs in about 7% of people. The median (average) overall survival is about 6 months.

Newer treatments will likely improve the survival rate as they gain approval. People with a diagnosis of refractory or relapsed DLBCL may want to discuss clinical trial options with an oncologist.

Participating in studies can help researchers find new and improved options.

People with refractory and relapsed DLBCL have an overall less favorable outlook. Several treatment options are available that can help reduce disease activity or achieve remission.

Researchers continue to look into new treatment methods. These may help improve effectiveness in future treatment options.

Individuals living with DLBCL may want to discuss participating in clinical trials testing novel treatments. Trials help determine safety and effectiveness and can lead to newer, improved therapies.