Early vs. Advanced DLBCL: How Are They Treated Differently? | MyLymphomaTeam

Connect with others who understand.

sign up Log in
Resources
About MyLymphomaTeam
Powered By

Early vs. Advanced DLBCL: How Are They Treated Differently?

Medically reviewed by Leonora Valdez, M.D.
Updated on March 25, 2024

  • Diffuse large B-cell lymphoma (DLBCL) is staged based on which lymph nodes and organs are involved. If the disease has spread, it’s considered more advanced.
  • Advanced DLBCL is usually treated with a combination of chemotherapy and immunotherapy drugs.
  • Radiation therapy and other drug options may be recommended in specific cases of advanced DLBCL.

As with many cancers, diagnosing diffuse large B-cell lymphoma involves staging to help determine its extent or spread. DLBCL is a fast-growing blood cancer and the most common subtype of non-Hodgkin lymphoma. DLBCL is staged based on where the cancer is found in the body. Knowing the stage helps doctors recommend the most effective treatment options. Although DLBCL grows quickly, it can respond well to treatment, especially when it’s targeted to the correct stage.

Staging DLBCL

DLBCL affects your lymphatic system — the group of organs that help your immune system fight infections and support healthy fluid levels in your body. DLBCL staging is based on where cancer cells are found in the lymphatic system. The cells may show up in the lymph nodes (small, infection-fighting structures located throughout the body). Lymphoma can also occur in lymphoid organs such as the thymus, spleen, and tonsils.

DLBCL is divided into four stages, sometimes written with Roman numerals (e.g., stage I, stage IV):

  • Stage 1 — Lymphoma is in one area of lymph nodes or one lymphoid organ. One node region refers to a node or a group of nodes next to each other.
  • Stage 1E — Lymphoma starts in one organ outside the lymphatic system and is only in that extranodal (outside the lymph nodes) site. This is known as extranodal lymphoma. The organs in which DLBCL commonly starts outside the lymphatic system are the bones or bone marrow, brain or spinal cord, and gastrointestinal tract.
  • Stage 2 — Lymphoma is in two or more lymph node regions in only the upper half (above the diaphragm) or lower half (below the diaphragm) of the body.
  • Stage 2E — Lymphoma affects one organ outside the lymphatic system and is also in at least one group of lymph nodes in only the upper or lower half of the body.
  • Stage 3 — Lymphoma is in lymph nodes in both the upper and lower halves of the body or only above the diaphragm but involves the spleen.
  • Stage 4 — Lymphoma starts in a group of lymph nodes and has spread to additional extranodal sites.

Although some aspects of treatment are similar in DLBCL regardless of stage, the use of certain drugs or radiation varies by stage and prognosis (outlook). Doctors use a tool called the International Prognostic Index (IPI) to better understand the outlook for DLBCL.

The IPI helps determine how serious diffuse large B-cell lymphoma (DLBCL) is. It considers factors like your age, the stage of your lymphoma, whether organs outside the lymphatic system are involved, your performance status (how well you can do daily activities), and the level of lactate dehydrogenase (LDH) in your body. LDH is a protein in your blood that can increase as lymphoma progresses.

A higher IPI score means that the disease has a worse outlook. Factors that make DLBCL higher risk include age above 60 years, stage 3 or 4 disease, lymphoma in more than one organ outside the lymph nodes, low performance status, and a high LDH level.

Read more about prognosis and survival rates with DLBCL.

Treating Early-Stage DLBCL

DLBCL is considered early when it’s either stage 1 or 2. For the past 20 years, first-line (used as the first option) treatment of DLBCL has been a combination of drugs called R-CHOP. The R-CHOP regimen consists of:

Three to six cycles of R-CHOP treatment alone are generally considered an acceptable treatment for early-stage DLBCL. Each 21-day R-CHOP cycle includes five days of chemotherapy followed by a rest period. Per a 2021 study in the American Journal of Hematology, R-CHOP has the potential to cure disease in 60 percent of people with acquired DLBCL — cancer that doesn’t run in families.

Six cycles of chemotherapy with the R-CHOP regimen are usually the first-line treatment for early-stage DLBCL.

Enter Cell 2 Content Here...

Enter Cell 3 Content Here...

Enter Cell 4 Content Here...

Enter Cell 5 Content Here...

Enter Cell 6 Content Here...

Rituximab is a monoclonal antibody, a type of immunotherapy that has a specific treatment target and less toxicity (fewer side effects). Monoclonal antibodies act like the body’s naturally occurring antibodies — proteins in the immune system that mark other proteins for destruction by immune cells.

Cyclophosphamide, vincristine, and doxorubicin are standard chemotherapy drugs, which kill fast-growing cells. Although the main target is cancer cells, fast-growing healthy cells are also affected (healthy blood cells, hair, nails, mucous membranes). Death of healthy cells results in the side effects seen with standard chemotherapy.

Prednisone is a steroid, a type of drug that reduces inflammation — and therefore some of the side effects — by suppressing the immune system.

Treating Advanced Stage DLBCL

DLBCL is considered advanced when it’s either stage 3 or 4. Because DLBCL grows so fast, 60 percent to 70 percent of people have advanced DLBCL by the time they’re diagnosed. Treatment options include chemotherapy combined with immunotherapy (drugs that use the immune system to treat disease) and radiation therapy. Six rounds of R-CHOP are considered the first-line treatment for advanced DLBCL. This means it’s the first treatment option doctors recommend for this stage.

DLBCL is considered advanced when it’s either stage 3 or stage 4.

Enter Cell 2 Content Here...

Enter Cell 3 Content Here...

Enter Cell 4 Content Here...

Enter Cell 5 Content Here...

Enter Cell 6 Content Here...

If your DLBCL doesn’t have a complete response (go away completely) after first-line chemotherapy, your oncologist will try other chemotherapy drug combinations, sometimes including rituximab.

Pola-R-CHP

The U.S. Food and Drug Administration (FDA) has approved Pola-R-CHP as another first-line treatment option for previously untreated advanced DLBCL. This drug combination consists of polatuzumab vedotin-piiq (Polivy) plus rituximab, cyclophosphamide, doxorubicin, and prednisone. Like rituximab, polatuzumab vedotin-piiq is a monoclonal antibody. The FDA based its approval on a 2022 clinical trial in which 879 people were treated with either Pola-R-CHP or R-CHOP.

In the study, the risks of death, relapse (return of a disease after initial improvement with treatment), and worsening of disease were lower in people receiving Pola-R-CHP. As with R-CHOP, six cycles of Pola-R-CHP are given to treat advanced DLBCL.

Read more about the risk of relapse in DLBCL.

Radiation Therapy

Although radiation therapy is commonly part of early-stage DLBCL treatment, it’s generally used only in specific cases of advanced disease. Based on available clinical trials, radiation therapy is recommended for people with DLBCL who have bulky disease.

Bulky disease refers to lymphoma in which the largest tumor is more than 10 centimeters wide. In DLBCL, radiation is sometimes used even when the largest tumor is more than 7.5 centimeters wide. If you have advanced DLBCL without bulky disease, you may be offered radiation if a small amount of disease has spread to your bones.

Chemotherapy To Prevent Central Nervous System Relapse

If you’re at increased risk of a DLBCL relapse, that may guide your doctor’s recommendations for treatment options. A higher IPI score means a higher risk of relapse.

Some people with DLBCL are more likely to have their disease relapse in the central nervous system (CNS), which consists of the brain and spinal cord. They may be offered a chemotherapy injection directly into the fluid around the spinal cord. To prevent CNS relapse, methotrexate, a chemotherapy drug that stops cancer cells from producing faulty DNA, is sometimes given in addition to chemotherapy.

Bone Marrow Transplant

For people who are younger and have high-risk DLBCL based on IPI score, a bone marrow transplant is a second-line treatment option. That said, bone marrow transplants are not known to work unless DLBCL improves with chemotherapy.

CAR T-Cell Therapy

If DLBCL relapses after first-line therapy or if the patient is not a good candidate for transplant, chimeric antigen receptor (CAR) T-cell therapy may be an option. CAR T-cell therapy trains the T cells in your immune system to recognize and destroy cancer cells. In CAR T-cell therapy, immune cells called T cells are collected from your blood, genetically engineered to recognize lymphoma cells, and returned to your body to fight cancer.

If you relapsed within one year of receiving R-CHOP therapy or have refractory disease, your oncologist may suggest CAR T-cell therapy. Some examples of CAR T-cell therapy include:

Bispecific Antibodies

In 2023, two bispecific antibodies were approved 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 cells.

Bispecific antibodies approved to treat relapsed or refractory DLBCL include:

  • Epcoritamab-bysp (Epkinly)
  • Glofitamab-gxbm (Columvi)

Other new drugs approved for DLBCL include loncastuximab tesirine-lpylm (Zylonta).

Clinical Trials

If you or someone you love has been diagnosed with advanced DLBCL, it may be worthwhile to get involved in a clinical trial. This is especially true if the cancer hasn’t responded to first-line or second-line treatment.

Joining a clinical study may provide you with access to new treatments currently being tested.

Enter Cell 2 Content Here...

Enter Cell 3 Content Here...

Enter Cell 4 Content Here...

Enter Cell 5 Content Here...

Enter Cell 6 Content Here...

Based on discoveries about genetic changes in DLBCL, researchers are looking at new targeted therapies (treatments aimed directly at cancer cells) and immunotherapies (treatments that boost the body’s immune system). Doctors are also researching new ways to combine chemotherapy drugs for the best survival results. If you’re interested in learning more about clinical studies in which you may be eligible to participate, ask your oncologist for more information.

Talk With Others Who Understand

MyLymphomaTeam is the social network for people with lymphoma and their loved ones. Here, more than 17,000 members who understand what it’s like to face lymphoma gather to provide support and answers.

Have you been diagnosed with DLBCL? What stage is your lymphoma, and which treatments have you received? Share your experience below, or post a comment on your Activities page to start a conversation.

References
  1. Staging of Lymphoma — Lymphoma Action
  2. Diffuse Large B-Cell Lymphoma — StatPearls
  3. Diffuse Large B-Cell Lymphoma — Cleveland Clinic
  4. Diffuse Large B-Cell Lymphoma — Canadian Cancer Society
  5. 2021 Update on Diffuse Large B Cell Lymphoma: A Review of Current Data and Potential Applications on Risk Stratification and Management — American Journal of Hematology
  6. Survival Rates and Factors That Affect Prognosis (Outlook) for Non-Hodgkin Lymphoma — American Cancer Society
  7. Limited-Stage Diffuse Large B-Cell Lymphoma — Blood
  8. Treating B-Cell Non-Hodgkin Lymphoma — American Cancer Society
  9. Diffuse Large B-Cell Lymphoma — Lymphoma Action
  10. Cyclophosphamide — StatPearls
  11. Vincristine — StatPearls
  12. Doxorubicin — StatPearls
  13. How Chemotherapy Drugs Work — American Cancer Society
  14. Monoclonal Antibodies and Their Side Effects — American Cancer Society
  15. FDA Approves Polatuzumab Vedotin Plus R-CHP for Previously Untreated DLBCL — OncLive
  16. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma — The New England Journal of Medicine
  17. The Evolving Role of Radiation Therapy in DLBCL: From Early-Stage to Refractory Disease — Oncology
  18. Limited-Stage DLBCL: It’s Patient Selection — Blood
  19. CAR T-Cell Therapy and Its Side Effects — American Cancer Society
  20. The New Algorithm for Second-Line Large B-Cell Lymphoma Treatment — Targeted Oncology
  21. Clinical Trials — American Cancer Society
  22. Role of Bispecific Antibodies in Relapsed/Refractory Diffuse Large B-Cell Lymphoma in the CART Era — Frontiers in Immunology
  23. Epkinly Approved for Relapsed, Refractory Diffuse Large B-Cell Lymphoma — Medical Professionals Reference
  24. Columvi Approved for Relapsed or Refractory Diffuse Large B-Cell Lymphoma — Medical Professionals Reference

Updated on March 25, 2024
All updates must be accompanied by text or a picture.

We'd love to hear from you! Please share your name and email to post and read comments.

You'll also get the latest articles directly to your inbox.

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Leonora Valdez, M.D. received her medical degree from the Autonomous University of Guadalajara before pursuing a fellowship in internal medicine and subsequently in medical oncology at the National Cancer Institute. Learn more about her here.
Chelsea Alvarado, M.D. earned her Bachelor of Science in biochemistry from Temple University in Philadelphia, Pennsylvania, and her Doctor of Medicine from the University of Maryland School of Medicine in Baltimore, Maryland. Learn more about her here.

Related Articles

When treatment for diffuse large B-cell lymphoma (DLBCL) successfully kills all of your detectabl...

Remission and Complete Response in DLBCL: How Long It Lasts and More

When treatment for diffuse large B-cell lymphoma (DLBCL) successfully kills all of your detectabl...
Roughly 50 percent to 60 percent of people relapse within the first two years of achieving remiss...

DLBCL Relapse Chances and Treatment Options

Roughly 50 percent to 60 percent of people relapse within the first two years of achieving remiss...
Burkitt lymphoma is a type of non-Hodgkin lymphoma (NHL) that grows very quickly. People who are...

Burkitt Lymphoma: Treatments and Side Effects

Burkitt lymphoma is a type of non-Hodgkin lymphoma (NHL) that grows very quickly. People who are...
Non-Hodgkin lymphoma (NHL) takes dozens of different forms, and there are many treatment options...

Non-Hodgkin Lymphoma Treatment: What You Need To Know

Non-Hodgkin lymphoma (NHL) takes dozens of different forms, and there are many treatment options...
Undergoing lymphoma treatment can sometimes bring along harsh side effects, including digestive ...

Managing Lymphoma Treatment Side Effects

Undergoing lymphoma treatment can sometimes bring along harsh side effects, including digestive ...
For many people diagnosed with certain types of non-Hodgkin lymphoma (NHL), it’s recommended to “...

Watchful Waiting With Non-Hodgkin Lymphoma (NHL)

For many people diagnosed with certain types of non-Hodgkin lymphoma (NHL), it’s recommended to “...

Recent Articles

MyHealthTeam does not provide health services, and if you need help, we’d strongly encourage you ...

Crisis Resources

MyHealthTeam does not provide health services, and if you need help, we’d strongly encourage you ...
You are the key opinion leader of your disease — this was the sentiment shared by speakers in a p...

6 Ways To Advocate for Your Lymphoma Care According to Health Care Professionals

You are the key opinion leader of your disease — this was the sentiment shared by speakers in a p...
No one knows what it’s like to have cancer unless they’ve actually been through it. Lou Lanza is ...

5 Suggestions To Ease Your Cancer Journey From a Lymphoma Advocate

No one knows what it’s like to have cancer unless they’ve actually been through it. Lou Lanza is ...
After successful treatment for diffuse large B-cell lymphoma (DLBCL), you’ll enter complete remis...

DLBCL Relapse: 4 Symptoms To Watch For

After successful treatment for diffuse large B-cell lymphoma (DLBCL), you’ll enter complete remis...
Double-hit lymphoma (DHL) is an aggressive cancer that develops from white blood cells called B l...

Double-Hit Lymphoma in DLBCL: Symptoms, Survival Rate, and More

Double-hit lymphoma (DHL) is an aggressive cancer that develops from white blood cells called B l...
The majority of people with diffuse large B-cell lymphoma (DLBCL) will live with their condition ...

DLBCL Prognosis: Fear, Hope, and Understanding Survival Rates

The majority of people with diffuse large B-cell lymphoma (DLBCL) will live with their condition ...
MyLymphomaTeam My lymphoma Team

Thank you for subscribing!

Become a member to get even more:

sign up for free

close