Navigating Relapse
- A relapse of diffuse large B-cell lymphoma (DLBCL) means the cancer has returned after initial treatment, most often within the first two years.
- Acting quickly to confirm the relapse and consulting a lymphoma specialist can make a significant difference in outcomes.
- New therapies, including CAR T-Cell Therapy and bispecific antibodies, have dramatically improved the outcomes for patients with relapsed or refractory DLBCL.
When Diffuse Large B-Cell Lymphoma Comes Back
Hearing that lymphoma has returned can be one of the most challenging moments in a cancer journey but does not mean the end. Leading lymphoma doctors now say the playbook for relapsed diffuse large B-cell lymphoma, the most common type of non-Hodgkin lymphoma, has changed as powerful new immunotherapies are giving patients second and even third chances at remission.“For most patients with diffuse large B-cell lymphoma and other aggressive lymphomas, they will receive this, they’ll go into remission and the disease won’t come back,” says Dr. Jonathon Cohen, a professor of hematology and medical oncology at Emory University School of Medicine and the Winship Cancer Institute, before adding, “For the patients where the disease does come back, historically we would use more chemotherapy and potentially something called a stem cell transplant… However, we’ve identified additional approaches including CAR T-Cell Therapy, which is an immune treatment where we collect a patient’s T-cells and they are then engineered in a way that they recognize the lymphoma and then we can infuse them back into the patient where they attack the lymphoma cells and reinduce a remission.”
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A Playbook for Facing a Relapse
Step One: Confirm the Relapse
If symptoms such as swollen lymph nodes, fever, night sweats, or unexplained weight loss return after remission, the first step is confirming that the lymphoma has truly come back. This typically involves:
- Biopsy: To confirm lymphoma rather than infection or inflammation, and to evaluate molecular features that can guide treatment.
- PET/CT Imaging: To determine the extent of disease.
Step Two: See a Lymphoma Specialist
Early consultation with a lymphoma specialist is essential. Treatment decisions at relapse are highly individualized and depend on factors such as the timing of the relapse, prior therapies, molecular characteristics from the biopsy, the aggressiveness of the lymphoma, and the patient’s overall health and other medical conditions.
Step Three: Understand Treatment Options
Treatment strategies depend on the patient’s history and disease characteristics.
Non-Hodgkin Lymphoma Resources
- CAR T-Cell Therapy Explained: What Diffuse Large B-Cell Lymphoma Patients Should Know
- CAR T-Cell Therapy Side Effects Can Be Serious, But Many Are Short-Lived
- CAR T-Cell Therapy for Non-Hodgkin Lymphoma
- Bispecific Antibodies vs. CAR T-Cell Therapy: What Are the Differences Non-Hodgkin Lymphoma Patients Need to Know?
- CAR-T Therapy is a Game-Changer for Common Type of Non-Hodgkin Lymphoma
- Could New Non-Hodgkin Lymphoma Drugs Mean Less Chemo in the Future?
CAR T-Cell Therapy
CAR T‑Cell Therapy uses a patient’s own T cells, which are modified in the lab to recognize and attack lymphoma cells. It is approved for relapsed or refractory DLBCL after at least two prior therapies or if it came back within 12 months. The approved products include axi‑cel (Yescarta), liso‑cel (Breyanzi), and tisa‑cel (Kymriah). Across clinical trials, overall response rates range from about 60-80%, with complete response rates of roughly 40-55%, depending on the product and patient population. Overall survival at two years is approximately 40-50%, though individual outcomes vary based on factors such as age, disease characteristics, and prior treatments.
Bispecific Antibodies
For patients who relapse after CAR T‑Cell Therapy or are not candidates for it, bispecific antibodies offer an effective treatment option. These therapies, such as epcoritamab (Epkinly) and glofitamab (Columvi), simultaneously bind lymphoma cells and immune system T cells, bringing T cells into proximity with cancer cells to trigger targeted immune mediated killing. In clinical studies of relapsed or refractory DLBCL, overall response rates range from 50-65%, with complete response rates of 35-45%, depending on the specific drug and patient population. Among patients who have previously received CAR T‑Cell Therapy, a group historically with very limited options, bispecific antibodies demonstrate meaningful activity, with overall response rates of approximately 50-60% and complete response rates of 30–40%, though smaller studies in selected patients have reported somewhat higher complete response rates.
Stem Cell Transplant
For some patients, an autologous stem cell transplant can still be a treatment option, especially if the lymphoma responds well to repeat chemotherapy. Patients receive high dose chemotherapy to attack the cancer, followed by infusion (transplant) of their own previously collected stem cells to help the blood and immune system recover. This is usually considered when the lymphoma returns after a long period of remission. Historically, it was the standard treatment for eligible patients before newer therapies, like CAR T-Cell Therapy, became widely available.
Other potential strategies include:
- Monoclonal antibodies: Tafasitamab can be used, sometimes in combination with lenalidomide, to help the immune system attack lymphoma cells.
- Antibody-drug conjugates: Loncastuximab tesirine and brentuximab vedotin deliver chemotherapy directly to lymphoma cells, helping to limit damage to normal cells.
- Clinical trials: Patients may also have access to next-generation CAR T-Cell Therapies or other novel immunotherapies that are not yet widely available.
Because each patient’s disease and treatment history are unique, working closely with a lymphoma specialist is essential to determine the best sequence of therapies and maximize the chance of long-term remission.
Questions to Ask Your Doctor:
- How do you confirm that my lymphoma has returned?
- What subtype or molecular features does my lymphoma have, and how do they affect treatment choices?
- Which treatments are most appropriate for me given my prior therapies and current health?
- Am I a candidate for CAR T-Cell Therapy, bispecific antibodies, or a stem cell transplant? What are the potential benefits and risks of each option?
- Are there clinical trials I might consider?
- How will we monitor my response to treatment?
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