Diffuse Large B-Cell Lymphoma Recurrent

When diffuse large B-cell lymphoma returns after treatment, it presents new challenges—but also new treatment options. Understanding relapse, recognizing the signs, and knowing what therapies are available can make a significant difference in managing this aggressive blood cancer.

Table of contents

• What is Relapsed or Refractory DLBCL?
• How Common is Relapse?
• Symptoms of Recurrent DLBCL
• Treatment Options for Relapsed or Refractory DLBCL
• Understanding Your Outlook

What is Relapsed or Refractory DLBCL?

The term relapsed refers to disease that reappears or grows again after a period of remission (when there are no signs of lymphoma in your body). The term refractory is used to describe when the lymphoma does not respond to treatment, meaning that the cancer cells continue to grow, or when the response to treatment does not last very long.^[2]

After successful treatment for diffuse large B-cell lymphoma, many people achieve complete remission. During this time, there are no signs of lymphoma in the body and you have no symptoms. Some people achieve only partial remission, where there are still some lymphoma cells and you may have some symptoms, but the cancer is affecting fewer areas of your body than before.^[4]

How Common is Relapse?

Overall, around 40% of patients with diffuse large B-cell lymphoma have refractory disease or relapse after the first line of treatment. This includes about 15 to 20% who have refractory disease and 20 to 30% who relapse after initially responding to treatment.^[5]

The type of response you have to your first round of treatment affects your risk of the lymphoma returning. The complete response rate after the standard R-CHOP treatment (rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone) is roughly 75 percent. Studies show that those who achieve complete response have the best outlook and a low relapse rate.^[4]

It is estimated that about one-third of people who achieve complete response after initial treatment with R-CHOP will relapse within two years of treatment. The chances of the lymphoma returning are lower the longer you stay in remission. Another 20 percent of people achieve only partial response, and their DLBCL becomes resistant to R-CHOP treatment.^[4]

Symptoms of Recurrent DLBCL

Research shows that most people experience symptoms during a DLBCL relapse. One study found that 67 percent of participants were experiencing symptoms when they were diagnosed with a relapse. Most relapse symptoms are similar to the ones experienced before initial diagnosis.^[4]

The most common symptom is swollen or enlarged lymph nodes, which appear as lumps that can be felt underneath your skin. These are often painless but may continue to grow. You may notice them in your neck, armpits, or groin.^[18]

Swelling can also occur in lymph nodes deeper within your body. This can cause abdominal pain, commonly in the lower right side, but it can spread to other areas as well. This pain may be accompanied by nausea, vomiting, diarrhea, or fever.^[18]

Some people with relapsed DLBCL experience B symptoms, which include a fever above 103 degrees Fahrenheit that lasts longer than two days or comes and goes, unexplained weight loss involving more than 10% of your body weight over six months, and heavy night sweats so intense that they drench your sheets.^[1]

You should contact your healthcare provider if you notice swollen lymph nodes for several weeks or if they continue to grow, or if you notice other signs that suggest the lymphoma may be returning.^[18]

Treatment Options for Relapsed or Refractory DLBCL

Before starting a second line of treatment, it is recommended to repeat the tumor biopsy. This helps confirm that findings on scans represent actual disease rather than false-positive results, and it helps exclude other diseases or changes in the type of lymphoma.^[5]

High-Dose Chemotherapy and Stem Cell Transplantation

High-dose chemotherapy followed by stem cell transplantation can be used to treat patients with DLBCL whose disease is refractory or relapsed following initial chemotherapy. The majority of patients undergoing stem cell transplantation will have an autologous transplant, meaning the patient receives their own stem cells that were collected prior to the procedure. Occasionally, a patient will undergo an allogeneic transplant, where the patient receives stem cells from a donor.^[2]

Second-Line Chemotherapy Regimens

For patients with relapsed or refractory disease, several combination chemotherapy regimens are available. These second-line regimens include:^[2]

• Ifosfamide, carboplatin, and etoposide (ICE)
• Dexamethasone, cisplatin, and cytarabine (DHAP)
• Gemcitabine-based therapy
• Bendamustine (Treanda) plus rituximab (Rituxan)
• Lenalidomide (Revlimid) plus rituximab (Rituxan)
• Polatuzumab vedotin-piiq (Polivy)
• Selinexor (Xpovio)
• Tafasitamab-cxix (Monjuvi)
• Epcoritamab-bysp (Epkinly)
• Glofitamab-gxbm (Columvi)

Recent studies have shown that the combination of polatuzumab vedotin with bendamustine and rituximab, and tafasitamab with lenalidomide, are approved options for patients who are not candidates for transplant. These combinations provide more effective options than conventional chemotherapy alone and have manageable side effect profiles.^[5]

CAR T-Cell Therapy

For some patients with relapsed or refractory disease, a form of immunotherapy called chimeric antigen receptor (CAR) T-cell therapy may be a possible treatment option. CAR T-cell therapy has become the new standard treatment for patients with refractory or early relapsed DLBCL, based on the positive results of clinical trials.^[5]

The approved CAR T-cell therapies include:^[2]

• Axicabtagene ciloleucel (Yescarta)
• Lisocabtagene maraleucel (liso-cel, Breyanzi)
• Tisagenlecleucel (Kymriah)

Treatment for Specific Subtypes

For patients who have a subset of DLBCL called primary mediastinal large B-cell lymphoma (PMBCL), second-line treatment regimens include pembrolizumab (Keytruda).^[2]

Understanding Your Outlook

Until relatively recently, the outlook for patients with relapsed or refractory DLBCL was very poor and treatment options were very limited. In recent years, several novel therapies have been approved that provide more effective options than conventional chemotherapy and have manageable side effect profiles.^[5]

Medical researchers are studying different treatments for DLBCL that comes back. Treatment options now include newer immunotherapies, targeted therapies, and CAR T-cell therapy, which have shown promising results for select patient groups.^[1]

The specific outlook depends on several factors, including how well you responded to first-line treatment, how long you have been in remission, and which treatment options are available to you. Your healthcare team can help you understand your individual situation and the best treatment approach for your specific case.^[4]

Some people experience further cycles of treatment, improvement, and relapse. It is important to work closely with your medical team and seek support when needed. Resources are available through organizations that specialize in lymphoma support and education.^[2]