If you’ve achieved remission after successful treatment for diffuse large B-cell lymphoma (DLBCL), you’re may wonder what the chances are of your cancer relapsing. Several factors influence your risk of a DLBCL relapse. It can feel scary and overwhelming to think about your cancer returning, but it’s important to understand the risks and be aware of the potential symptoms of a relapse.

If your DLBCL returns, your oncologist will recommend one of several treatment options. The treatment they choose will likely depend on what you’ve previously received. In this article, we’ll help you understand the risk of relapse and what treatment options are available for relapsed DLBCL.

First-Line Treatment for DLBCL

DLBCL is the most common subtype of non-Hodgkin lymphoma (NHL). The standard of care used as a first-line therapy or first round of treatment for DLBCL is R-CHOP, which derives its name from the medications in the regimen:

• Rituximab (Rituxan)
• Cyclophosphamide
• Doxorubicin — also known as hydroxydaunorubicin
• Vincristine (formerly sold as Oncovin)
• Prednisone

About one-third of people who achieve complete response after initial treatment with the R-CHOP regimen will relapse within two years of treatment.

R-CHOP is a regimen of chemoimmunotherapy that combines powerful chemotherapy and immunotherapy to prevent lymphoma cells from growing and dividing. After treatment with R-CHOP, you may achieve:

• Complete response or complete remission — There are no signs of lymphoma in your body, and you have no symptoms.
• Partial response or partial remission — There are still some lymphoma cells, and you may have some symptoms, but the cancer is affecting fewer areas of your body than before.

Understanding Your Risk for DLBCL Relapse

Several factors play a role in your risk for DLBCL relapse. They include how well you responded to the first round of treatment and how long you’ve been in remission. There’s also a chance that your DLBCL returns after you achieve a second remission. Some people experience further cycles of treatment, improvement, and relapse.

Initial Response to Treatment Affects Relapse Rate

The type of response you have to your first round of treatment affects your risk of your DLBCL returning. The complete response rate after R-CHOP treatment is roughly 75 percent. Studies show that those who achieve complete response have the best prognosis (outlook) and a low relapse rate.

The chances of your DLBCL returning are lower the longer you stay in remission.

It’s estimated that about one-third of people who achieve complete response after first-line treatment with R-CHOP will relapse within two years of treatment. Another 20 percent of people achieve only partial response, and their DLBCL becomes resistant to R-CHOP treatment. This form of the condition is known as primary refractory diffuse large B-cell lymphoma.

Sex and DLBCL Relapse Rates

Research from Wolters Kluwer UpToDate shows that males are more likely to develop DLBCL compared to females. Male sex is also associated with worse overall survival and a poor prognosis, as cited in an article from Archives of Medical Science. This means that fewer males than females are alive within a certain amount of time after receiving a DLBCL diagnosis or starting treatment.

One study found that males had worse relapse rates and progression-free survival (PFS). The term “PFS” refers to the amount of time a person lives with stable DLBCL that doesn’t progress or get worse. Together, these studies show that males have more relapses and that their disease is less stable than in females.

Read more about prognosis and survival rates with DLBCL.

Early and Late DLBCL Relapses

After achieving complete response after your first round of DLBCL treatment, your oncologist will follow up with you regularly to make sure your cancer hasn’t returned. The risk of DLBCL relapse is highest within the first two years of completing treatment and going into remission. If your DLBCL returns within this two-year window, it’s known as an early relapse.

Some people may see their DLBCL return after the two-year window — this is known as a late relapse. The rate of late relapses is lower than that for early relapses. One study of 847 people with DLBCL who achieved complete response for two years found that:

• 6.9 percent relapsed after three years
• 9.3 percent relapsed after five years
• 10.3 percent relapsed after eight years

This means the chances of your DLBCL returning are lower the longer you stay in remission.

Relapse After Second-Line and Later Treatments

If your DLBCL relapses, your oncologist will recommend a second-line treatment plan to help you reach remission again. Unfortunately, the chances of reaching a second remission are not as good.

A study from the British Journal of Cancer of more than 2,900 people with DLBCL investigated the rate of relapse after R-CHOP treatment. Researchers found that 538 (18 percent) of participants relapsed after the first round of treatment. Of those who relapsed, 208 (44 percent) responded to second-line treatment and achieved a second remission. A handful of participants also experienced a third relapse.

Treatments for relapsed DLBCL may include medication, bone marrow transplant, CAR T-cell therapy, or joining a clinical trial for a new therapy.

This study shows that it’s possible to continue to relapse after receiving several rounds of treatment and achieving remission. Your doctor will work with you to develop new treatment plans if your DLBCL returns after second- or third-line therapy.

Treatment After DLBCL Relapse

There are several second-line therapies available to treat relapsed DLBCL. The most common treatment is an autologous bone marrow transplant, but not everyone is a candidate for this procedure. You may also receive a combination of chemotherapy and immunotherapy to help you achieve a second or third remission.

Autologous Bone Marrow Transplant

If your cancer returns after R-CHOP therapy, your oncologist will likely recommend a bone marrow transplant as a second-line treatment. Bone marrow — the spongy tissue that fills your bones — contains cells that can create new, healthy blood cells. These transplants are common treatments for many blood cancers or hematological malignancies, including different types of lymphoma, leukemia, and myeloma.

During an autologous bone marrow transplant, healthy cells will be taken from your bone marrow or blood. In some cases, cells are taken from a healthy compatible donor instead. This is known as an allogeneic bone marrow transplant.

Then, your oncologist will treat you with high-dose chemotherapy — also referred to as salvage chemotherapy — to kill the lymphoma cells and create space in your bone marrow. After chemotherapy treatment is complete, the healthy cells are infused into your bloodstream. They travel to your bone marrow and begin making healthy blood cells.

Other Second-Line Treatment Options

Some people don’t respond well to salvage therapy, so they can’t receive a bone marrow transplant. For others, this procedure may be dangerous due to advanced age or other underlying health conditions. If you’re not eligible for a bone marrow transplant, your oncologist may recommend the following:

• Polatuzumab vedotin-piiq (Polivy) with or without bendamustine and/or rituximab
• Gemcitabine plus oxaliplatin (GemOx) with or without rituximab
• Tafasitamab-cxix (Monjuvi) plus lenalidomide (Revlimid)

Third-Line Treatment Options

If your first two treatments for relapsed DLBCL aren’t effective, there are still several more lines of therapy available.

CAR T-Cell Therapy

Chimeric antigen receptor (CAR) T-cell therapy is a relatively new advancement in treating cancer. It’s a type of gene therapy that teaches your immune system to recognize and destroy cancer cells. In CAR T-cell therapy, your T cells are collected, genetically engineered to recognize lymphoma cells, and returned to your body to fight cancer.

Your oncologist may prescribe CAR T-cell therapy if you relapsed within one year of receiving R-CHOP therapy, if you have refractory disease, or as a third-line treatment. Examples of anti-CD19 therapies approved for treating DLBCL include:

• Axicabtagene ciloleucel (Yescarta)
• Lisocabtagene maraleucel (Breyanzi)
• Tisagenlecleucel (Kymriah)

Bispecific Antibodies

In 2023, the U.S. Food and Drug Administration (FDA) approved two bispecific antibodies to treat relapsed/refractory DLBCL that hasn’t responded to other treatments. Bispecific antibodies are a new type of drug with two parts. One part of the drug recognizes and binds to cancer cells, while the other part attacks and kills the cancer cell.

Bispecific antibodies approved to treat relapsed or refractory DLBCL include apcoritamab-bysp (Epkinly) and glofitamab-gxbm (Columvi).

Other drugs approved for relapsed/refractory DLBCL in certain situations include Selinexor (Xpovio) and loncastuximab tesirine-lpyl (Zynlonta).

Clinical Trials

If you’re interested in gaining access to experimental DLBCL treatments, you may consider joining an oncology clinical trial. Clinical trials can be an option at any point in DLBCL treatment but may be recommended if your DLBCL continues to relapse after trying a second- or third-line treatment. Doctors and researchers are investigating new targeted therapies and monoclonal antibodies (lab-engineered protein drugs) to treat relapsed DLBCL. To learn more about clinical trials, talk to your oncologist.

Find Your Team

On MyLymphomaTeam, the online social network for people with lymphoma and their loved ones, more than 20,000 members come together to ask questions, give advice, and share their stories with others who understand life with lymphoma.

Has your DLBCL returned after treatment? What second- or third-line therapies have you received? Share your experience in the comments below, or start a conversation by posting on your Activities page.