B-Cell Lymphoma Recurrent

When B-cell lymphoma returns after successful treatment, it presents new challenges that require specialized care and treatment approaches to manage the disease effectively.

Table of contents

• Understanding Recurrent B-Cell Lymphoma
• Recognizing Symptoms of Recurrence
• When Relapse Occurs
• Treatment Options for Recurrent Disease
• Outlook After Recurrence

Understanding Recurrent B-Cell Lymphoma

B-cell lymphoma can come back after initial treatment, even when the first round of therapy puts the disease into remission (a period when there are no signs of cancer in the body). This return of the disease is called a recurrence or relapse. Treatment can cure some types of B-cell lymphoma and put the conditions into remission, but the conditions can come back (recur).^[1]

Doctors use the term “relapsed” to describe disease that reappears or grows again after a period of remission. Usually, doctors say that lymphoma has relapsed if it returns after successful treatment, meaning you have had a remission with no evidence of lymphoma on tests and scans that lasts for at least 6 months after treatment.^[5]

Relapse can happen if there are lymphoma cells left in your body after treatment.^[5] Between 30 percent and 40 percent of people with diffuse large B-cell lymphoma (DLBCL), the most common form of B-cell lymphoma, will experience their cancer returning within two years of finishing treatment.^[3]

Recognizing Symptoms of Recurrence

Most people experience symptoms when their B-cell lymphoma relapses. Research shows that 67 percent of people were experiencing symptoms when they were diagnosed with a relapse.^[3] Most relapse symptoms are similar to the ones experienced before the initial diagnosis.

Swollen or enlarged lymph nodes (small structures that belong to your immune system) may be a sign of B-cell lymphoma relapse. These appear as lumps that can be felt underneath your skin and are often painless. Lymph nodes can be found all over your body, but most people are familiar with the ones found in the neck, groin, and armpits. You may want to see your doctor if your lymph nodes are swollen for several weeks or continue to grow, or if you notice other signs of the disease coming back.^[3]

Swelling can also occur in the nodes deeper within your body, not just underneath your skin. Mesenteric lymphadenitis refers to swollen, inflamed lymph nodes that can cause pain in the abdomen (stomach), commonly in the lower right side, but it can spread out onto other areas as well.^[3]

Other symptoms that may indicate recurrent B-cell lymphoma include abdominal pain that doesn’t go away or gets worse, drenching night sweats, and fatigue.^[1]

When Relapse Occurs

The timing of relapse matters. Doctors distinguish between early and late relapses when B-cell lymphoma returns. Early relapse occurs less than two years after diagnosis, while late relapse happens more than two years after diagnosis.^[4]

For patients diagnosed with stage I-II DLBCL who achieve complete response or unconfirmed complete response after first-line treatment with immunochemotherapy (treatment that combines chemotherapy with drugs that boost the immune system), 12.2% eventually relapsed in one study. Of these patients, nine had early relapse and three experienced late relapse. The median time from diagnosis to relapse was 0.61 years for patients with early relapse and 3.66 years for patients with late relapse.^[4]

The chances of your B-cell lymphoma 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 (a standard chemotherapy regimen) will relapse within two years of treatment.^[9]

Treatment Options for Recurrent Disease

When B-cell lymphoma recurs, several treatment options are available. The treatment your doctor recommends will likely depend on what you’ve previously received and how your disease responded to earlier therapy.

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 (patient receives his or her own stem cells, collected prior to the procedure). Occasionally, a patient will undergo an allogeneic transplant (patient receives stem cells from a donor).^[8]

For relapsed or refractory patients, several combination chemotherapy regimens are available. These second-line regimens include ifosfamide, carboplatin, and etoposide (ICE); dexamethasone, cisplatin, and cytarabine (DHAP); gemcitabine-based therapy; bendamustine plus rituximab; and lenalidomide plus rituximab.^[8]

Other approved treatment options for relapsed or refractory disease include polatuzumab vedotin-piiq, selinexor, tafasitamab-cxix, epcoritamab-bysp, and glofitamab-gxbm.^[8]

For some relapsed or refractory patients, 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 positive results from clinical trials.^[7] The approved CAR T-cell therapies include axicabtagene ciloleucel, lisocabtagene maraleucel, and tisagenlecleucel.^[8]

Outlook After Recurrence

Patients who relapse after achieving remission face a challenging prognosis. The SCHOLAR-1 study, which established a benchmark for outcomes in relapsed or refractory DLBCL, identified an objective response rate of 26%, with only 7% achieving complete remission to treatment for relapsed or refractory disease. The median overall survival was 6.3 months, and the 2-year overall survival rate was only 20%.^[7]

In patients with stage I-II DLBCL who relapsed after first-line immunochemotherapy, the second complete response rate obtained was similar in late and early relapsing patients, being 33% versus 44% respectively. Three-year overall survival was 22% for early relapsing patients and 33% for late relapsing patients.^[4]

Overall, around 40% of patients with diffuse large B-cell lymphoma have refractory disease (15-20%) or relapse (20-30%) after the first line of treatment.^[7] However, recent advances, including CAR T-cell therapy and new targeted treatments, demonstrate promising efficacy for select patient groups.^[12]

In pivotal trials of CAR T-cell therapy, durable responses were achieved in approximately 40% to 50% of patients treated with these therapies, indicating that while many patients benefit, some will require subsequent treatment if the disease returns after CAR T-cell therapy.^[11]