What You Should Know About Relapsed or Refractory Follicular Lymphoma

Each person’s experience with follicular lymphoma (FL) is unique. Whether you’re living with FL or caring for someone who is, the physical, emotional and psychosocial effects can vary from person to person. No matter where you are in your experience, it’s important to know that help is available – and treatment options are continuing to expand.

Relapsed or Refractory FL

FL is a slow-growing form of non-Hodgkin’s lymphoma (NHL). Many patients with FL have no obvious symptoms of the disease at first. By the time signs and symptoms appear, the disease may already be at a more advanced stage (stage 3 or 4).1 The encouraging news is that initial treatments often work well, and patients can experience long periods of remission. However, for many patients, the lymphoma can return after treatment or it may stop responding to treatment.2 When this happens, the disease is known as “relapsed” or “refractory” (R/R) FL.3

In some cases, FL can turn into a more aggressive disease. Risk of FL transformation to DLBCL varies; in one study, the rate of transformation was 16% at 10 years.4,5,6 About one in five people diagnosed with FL will experience disease progression within the first two years of initial treatment.7

Treatments for R/R FL

For patients with FL whose disease has progressed or returned, your doctor may recommend another type of treatment. These may include:

• Chemoimmunotherapy – A combination treatment that uses chemotherapy, a treatment that kills cancer cells, and immunotherapy, which stimulates or boosts the immune system’s ability to recognize and destroy cancer cells8,9
• Radiation therapy – A type of treatment that uses beams of high-energy to abolish cancer cells and shrink tumors. It is also sometimes referred to as radiotherapy.10
• Monoclonal antibodies - Lab-produced molecules that serve as alternative antibodies that mimic the body's immune system to recognize, attack, and destroy cancer cells.9
• CAR T-cell therapy – A type of immunotherapy where a patient’s own T cells are genetically modified to recognize and attack cancer cells.9
• Bispecific antibodies – An antibody treatment that utilizes the power of your own immune system to help fight cancer by recognizing two different targets on cancer cells.9

“People living with follicular lymphoma know that they will live with this cancer for the rest of their lives, and many will eventually experience relapse,” says [advocacy organization spokesperson]. “The good news is that today, patients have a variety of treatment options available to them and research continues to show promise with new advances. This means that patients can make decisions with their care team based on their treatment history and what is most important to them.”

Treatment Options are Expanding

Recently, a class of therapies called bispecific antibodies have been approved for the treatment of R/R FL that has come back or that did not respond to previous treatment after receiving two or more treatments and may be an option for certain patients. Bispecific antibodies work with your immune system to help fight cancer.11 Bispecific antibody treatments are "off-the-shelf", meaning that they can be made available to treat patients soon after relapse or disease progression.12 This is particularly significant for patients who need urgent treatment.

“The introduction of bispecific antibodies for follicular lymphoma has been an important advancement for patients. Some of these treatments may also be administered until disease progression, which may help ensure the medicine keeps working in people's bodies, helping them maintain remission", says [community oncologist spokesperson]. “For those with relapsed or refractory follicular lymphoma, bispecific antibodies have also been proven to work in certain patients who were refractory to their last treatment, and patients whose disease has progressed within two years of first-line chemoimmunotherapy.”

One available bispecific antibody is EPKINLY® (epcoritamab-bysp). EPKINLY is a prescription medicine used to treat adults with certain types of DLBCL, high-grade B-cell lymphoma, or FL that has come back or that did not respond to previous treatment after receiving two or more treatments.13 In fact, it is the first and only bispecific treatment approved for both DLBCL and FL. EPKINLY is the only bispecific antibody administered subcutaneously (an injection given just under the skin), offering patients an innovative treatment option that may enable treatment at an oncologist's office.

EPKINLY works by targeting two cells in a patient’s body: T cells and B cells. T cells are immune cells that fight infection and disease. B cells are also immune cells, but some can become cancerous and grow uncontrollably in the body. EPKINLY binds these cells together so that the T cells can attack and destroy B cells.12

In clinical trials, 82% of FL patients who were treated with EPKINLY responded to treatment, with 60% of responders achieving a complete response, which means signs of cancer disappeared completely.13 Some patients achieved results in as few as 4 weeks (median (the number that is exactly in the middle of the range seen in the study) of 1.4 months; time varied from 1 to 3 months).13

The most common (≥20%) adverse reactions were injection site reactions, cytokine release syndrome (CRS), COVID-19, fatigue, upper respiratory tract infection, musculoskeletal pain, rash, diarrhea, fever, cough, and headache.13

Surrounding Yourself with Support

While every patient’s experience with FL may be different, there are resources to help.

“It’s important that patients, care partners, and their healthcare providers have the support and resources they need to navigate their unique treatment experiences,” said [Genmab spokesperson]. “MyNavCare Patient Support™ is one program that is available to patients who have been prescribed EPKINLY that provides comprehensive resources no matter where you are in your treatment experience, from disease information to financial assistance and live support.”

“A crucial factor in navigating a cancer diagnosis is finding a care team you feel comfortable with, so shared decision-making can take place and trust can be built,” shares [AbbVie spokesperson]. “Having open and honest conversations is key in a patient’s treatment journey.”

What is EPKINLY?13
EPKINLY is a prescription medicine used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, or follicular lymphoma (FL) that has come back or that did not respond to previous treatment after receiving 2 or more treatments. EPKINLY is approved based on patient response data. Studies are ongoing to confirm the clinical benefit of EPKINLY. It is not known if EPKINLY is safe and effective in children.

IMPORTANT SAFETY INFORMATION

Important Warnings—EPKINLY can cause serious side effects, including:

• Cytokine release syndrome (CRS), which is common during treatment with EPKINLY and can be serious or life-threatening. To help reduce your risk of CRS, you will receive EPKINLY on a step-up dosing schedule (when you receive 2 or 3 smaller step-up doses of EPKINLY before your first full dose during your first cycle of treatment), and you may also receive other medicines before and for 3 days after receiving EPKINLY. If your dose of EPKINLY is delayed for any reason, you may need to repeat the step-up dosing schedule.
• Neurologic problems that can be serious, and can be life-threatening and lead to death. Neurologic problems may happen days or weeks after you receive EPKINLY.

People with DLBCL or high-grade B-cell lymphoma should be hospitalized for 24 hours after receiving their first full dose of EPKINLY on day 15 of cycle 1 due to the risk of CRS and neurologic problems.

Tell your healthcare provider or get medical help right away if you develop a fever of 100.4°F (38°C) or higher; dizziness or lightheadedness; trouble breathing; chills; fast heartbeat; feeling anxious; headache; confusion; shaking (tremors); problems with balance and movement, such as trouble walking; trouble speaking or writing; confusion and disorientation; drowsiness, tiredness or lack of energy; muscle weakness; seizures; or memory loss. These may be symptoms of CRS or neurologic problems. If you have any symptoms that impair consciousness, do not drive or use heavy machinery or do other dangerous activities until your symptoms go away.

EPKINLY can cause other serious side effects, including:

• Infections that may lead to death. Your healthcare provider will check you for signs and symptoms of infection before and during treatment and treat you as needed if you develop an infection. You should receive medicines from your healthcare provider before you start treatment to help prevent infection. Tell your healthcare provider right away if you develop any symptoms of infection during treatment, including fever of 100.4°F (38°C) or higher, cough, chest pain, tiredness, shortness of breath, painful rash, sore throat, pain during urination, or feeling weak or generally unwell.
• Low blood cell counts, which can be serious or severe. Your healthcare provider will check your blood cell counts during treatment. EPKINLY may cause low blood cell counts, including low white blood cells (neutropenia), which can increase your risk for infection; low red blood cells (anemia), which can cause tiredness and shortness of breath; and low platelets (thrombocytopenia), which can cause bruising or bleeding problems.

Your healthcare provider will monitor you for symptoms of CRS, neurologic problems, infections, and low blood cell counts during treatment with EPKINLY. Your healthcare provider may temporarily stop or completely stop treatment with EPKINLY if you develop certain side effects.

Before you receive EPKINLY, tell your healthcare provider about all your medical conditions, including if you have an infection, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. If you receive EPKINLY while pregnant, it may harm your unborn baby. If you are a female who can become pregnant, your healthcare provider should do a pregnancy test before you start treatment with EPKINLY and you should use effective birth control (contraception) during treatment and for 4 months after your last dose of EPKINLY. Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment with EPKINLY. Do not breastfeed during treatment with EPKINLY and for 4 months after your last dose of EPKINLY.

In DLBCL or high-grade B-cell lymphoma, the most common side effects of EPKINLY include CRS, tiredness, muscle and bone pain, injection site reactions, fever, stomach-area (abdominal) pain, nausea, and diarrhea. The most common severe abnormal laboratory test results include decreased white blood cells, decreased red blood cells, and decreased platelets.

In follicular lymphoma the most common side effects of EPKINLY include injection site reactions, CRS, COVID-19, tiredness, upper respiratory tract infections, muscle and bone pain, rash, diarrhea, fever, cough, and headache. The most common severe abnormal laboratory test results include decreased white blood cells and decreased red blood cells.

These are not all of the possible side effects of EPKINLY. Call your doctor for medical advice about side effects.

You are encouraged to report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch or to Genmab US, Inc. at 1-855-4GENMAB (1-855-443-6622).

Please see Medication Guide, including Important Warnings.

1. Follicular Lymphoma. Lymphoma Action. https://lymphoma-action.org.uk/types-lymphoma-non-hodgkin-lymphoma/follicular-lymphoma#treatment. Accessed February 2025.
2. Follicular Lymphoma: Treatment Options. Lymphoma Research Foundation. https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/follicular-lymphoma/fltreatment/. Accessed March 2025.
3. Follicular Lymphoma: Relapsed/Refractory. Lymphoma Research Foundation. https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/follicular-lymphoma/relapsedfl/. Accessed February 2025.
4. Zheng W, Liu M, Guan L, Wang S. Outcomes of the transformation of follicular lymphoma to diffuse large B-cell lymphoma in the rituximab era: A population-based study. Cancer Med. 2024;13(8):e7120. doi:10.1002/cam4.7120
5. Al-Tourah AJ, Gill KK, Chhanabhai M, et al. Population -based analysis of incidence and outcome non-Hodgkin's lymphoma. J Clin Oncol. 2008 Nov 10; 26(32):5165-9. doi: 10.1200/JCO.2008.16. 2008 Oct 6. PMID: 18838711.
6. Batlevi CL, Sha F, Alperovich A, et al. Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups. Blood Cancer J. 2020;10(7):74. doi:10.1038/s41408-020-00340-z
7. Casulo, et al. Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study. J Clin Oncol. 2015 Jun 29;33(23):2516–2522. doi: 10.1200/JCO.2014.59.7534
8. Treatment Options: Chemotherapy. https://lymphoma.org/understanding-lymphoma/treatment-planning-and-options/treatments/chemotherapy/. Accessed March 2025.
9. Treatment Options: Immunotherapy. https://lymphoma.org/understanding-lymphoma/treatment-planning-and-options/treatments/immunotherapy/. Accessed March 2025.
10. Treatment Options: Radiation Therapy. https://lymphoma.org/understanding-lymphoma/treatment-planning-and-options/treatments/radiation/. Accessed March 2025.
11. Review of current status and prospects for bispecific antibodies. https://www.biochempeg.com/article/252.html. Accessed June 2025.
12. EPKINLY Patient Brochure. https://www.epkinly.com/content/dam/epcoritamab/docs/dlbcl-patient-brochure.pdf. Accessed March 2025.
13. EPKINLY [package insert]. Plainsboro, NJ: Genmab US, Inc. and North Chicago, IL: AbbVie Inc. 2023.

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