AbbVie Announces U.S. FDA Approval of EPKINLY® (epcoritamab-bysp) in Combination with Rituximab and Lenalidomide for Relapsed or Refractory Follicular Lymphoma

Rhea-AI Summary

AbbVie (NYSE: ABBV) announced U.S. FDA approval of EPKINLY (epcoritamab-bysp) in combination with rituximab and lenalidomide (EPKINLY + R2) for adult patients with relapsed or refractory follicular lymphoma after ≥1 prior systemic therapy.

The approval follows Phase 3 EPCORE FL-1 where EPKINLY + R2 reduced risk of progression or death by 79% (HR 0.21), achieved 89% ORR and 74% complete response, and median PFS was not reached versus 11.2 months for R2. Safety was consistent with known profiles; CRS occurred in 24% (mostly Grade 1–2).

Positive

• PFS risk reduction 79% (HR 0.21)
• Overall response rate 89% with EPKINLY + R2
• Complete response rate 74% with EPKINLY + R2
• Median PFS not reached versus 11.2 months for R2
• First FDA approval of a bispecific combination therapy in lymphoma

Negative

• Cytokine release syndrome occurred in 24% of patients
• Grade 3–4 lab abnormalities ≥10%: decreased neutrophils, lymphocytes, platelets
• Prescribing information includes Boxed Warning for CRS and ICANS

Insights

Clinical Oncology Strategist

FDA approved EPKINLY+R2 for R/R follicular lymphoma with strong Phase 3 PFS and CR benefits.

EPKINLY in combination with rituximab and lenalidomide produced a large clinical effect: a 79% reduction in risk of progression or death (HR 0.21, 95% CI: 0.13% - 0.33%, p<0.0001) and an overall response rate of 89% versus 74% for R2, with 74% complete responses versus 43%. Median PFS was not reached for the combination versus 11.2 months for R2, supporting meaningful durability of benefit in the trial population.

Safety aligns with known profiles: common adverse events included rash, infections, fatigue, injection site reactions, gastrointestinal effects, cytokine release syndrome (CRS) in 24% (mostly Grade 1–2), and one Grade 1 ICANS event. The approved label includes a Boxed Warning for serious CRS and ICANS and lists infections, cytopenias, and embryo-fetal toxicity as precautions. Clinicians should weigh the high efficacy signal against these immune-mediated risks when selecting patients and settings for outpatient subcutaneous administration.

Commercial Access Analyst

Approval establishes first bispecific antibody combination for second-line+ follicular lymphoma and expands EPKINLY indications.

This approval makes EPKINLY the first bispecific antibody available for follicular lymphoma in the second-line and later setting and converts its prior accelerated monotherapy approval to full approval based on confirmatory Phase 3 data. The regimen is fixed-duration and chemotherapy-free, which may broaden site-of-care options and patient acceptability because it can be administered subcutaneously in outpatient settings.

Key access considerations include management of CRS/ICANS given the Boxed Warning, payer review of comparative efficacy versus R2 given the large PFS and CR advantages, and timing of broader uptake ahead of planned presentations at the ASH meeting in December 2025. Watch regulatory filings outside the U.S. and real-world adoption metrics over the next 6–12 months as uptake and safety management practices become clearer.

-   EPKINLY plus rituximab and lenalidomide (EPKINLY + R²) is now the first and only bispecific antibody combination therapy available for patients with relapsed or refractory follicular lymphoma after at least one line of systemic therapy
-   In the Phase 3 EPCORE^® FL-1 trial, EPKINLY + R² demonstrated significantly superior progression-free survival and overall response rates compared to standard of care R²with approximately 3 out of 4 patients achieving a complete response
-   Approval marks third indication for EPKINLY and first-ever FDA approval for a bispecific combination therapy in lymphoma

NORTH CHICAGO, Ill., Nov. 18, 2025 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that EPKINLY^® (epcoritamab-bysp), a T-cell engaging bispecific antibody administered subcutaneously, in combination with rituximab and lenalidomide (EPKINLY + R²) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL). This approval of EPKINLY is based on results from the pivotal Phase 3 EPCORE^® FL-1 study that evaluated fixed duration EPKINLY + R² compared to standard of care R² and demonstrates the potential of this combination therapy to reshape FL treatment and to reach patients earlier in their treatment.ⁱ 

"Recurrent follicular lymphoma can be an incurable, complex and persistent disease, creating a clear need for additional treatments that can change its course earlier in the treatment journey," said Lorenzo Falchi, M.D., lymphoma specialist, department of medicine, Memorial Sloan Kettering Cancer Center. "The results shown with EPKINLY + R² in the EPCORE FL-1 study are incredibly meaningful, demonstrating durable responses compared to patients treated with R² alone. These data, delivered by a regimen that's chemotherapy-free and can be administered in the outpatient setting, suggest that EPKINLY + R² could potentially become a new standard of care."

FL is typically an indolent (slow-growing) form of non-Hodgkin lymphoma (NHL) that arises from B-lymphocytes and impacts approximately 15,000 new patients per year in the U.S.^ii,iii The disease is considered incurable with current available therapies.^iv Patients with FL often relapse, and in some cases, the disease can transform into a more aggressive form of NHL called diffuse large B-cell lymphoma (DLBCL).^v

The Phase 3 EPCORE FL-1 study included a broad range of patients, including those with indolent to aggressive disease. In the study, EPKINLY + R² reduced the risk of disease progression or death by 79% (HR 0.21, 95% CI: 0.13% - 0.33%, p<0.0001) compared to standard of care R² alone. In the dual primary endpoint of overall response rate (ORR), 89% of patients treated with EPKINLY + R² responded to treatment (n=216/243, 95% CI: 84% - 93%; p<0.0001) compared to 74% of patients treated with R² (n=181/245, 95% CI: 68%-79%). The median for dual primary endpoint of progression-free survival (PFS), was not reached (NR) among patients treated with EPKINLY + R² (95% CI: 21.9 months - NR) compared to 11.2 months for patients treated with R² (95% CI: 10.5 months - NR). Among patients who were treated with EPKINLY + R², 74% achieved a complete response (CR) (n=181/243, 95% CI: 69% - 80%, p<0.0001) compared to 43% of patients treated with R² (n=106/245, 95% CI: 37% - 50%).ⁱ

The safety profile of EPKINLY + R² in the EPCORE FL-1 study was generally consistent with the known safety profiles of the individual regimens (epcoritamab and R²).  The most common (≥ 20%) adverse reactions in patients who received EPKINLY + R² were rash, upper respiratory tract infections, fatigue, injection site reactions, constipation, diarrhea, cytokine release syndrome (CRS), pneumonia, COVID-19 and fever. The most common Grade 3 to 4 laboratory abnormalities (≥ 10%) were decreased neutrophil count, lymphocyte count, and platelets. CRS occurred in 24% of patients at the recommended 3 step-up dosage schedule, and was primarily low grade (19% Grade 1, 5% Grade 2). A single event of immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in one patient, grade 1 (0.8%). The prescribing information has a Boxed Warning for serious or life-threatening CRS and ICANS. Warnings and precautions include infections, cytopenias, and embryo-fetal toxicity. Please see additional Important Safety Information below.

"Today's milestone marks meaningful progress for people living with follicular lymphoma. With a bispecific-based therapy that can be administered in a variety of medical settings, patients have the possibility of accessing this treatment at sites of care closer to where they live," said Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation.

EPKINLY + R² was previously granted Breakthrough Therapy Designation (BTD) by the FDA for the treatment of R/R FL. This designation is an FDA process designed to expedite the development and review of drugs that are intended to treat a serious condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).

"With this approval, EPKINLY is now the first bispecific antibody available for patients with follicular lymphoma in the second-line plus setting. New options are needed to improve outcomes for patients with relapsed or refractory disease," said Daejin Abidoye, MD, vice president, therapeutic area head, oncology, solid tumor and hematology, AbbVie.

In June 2024, EPKINLY monotherapy was granted accelerated approval by the FDA for the treatment of R/R FL following two or more lines of systemic therapy. With the results of the confirmatory Phase 3 EPCORE FL-1 study, the FDA has also converted this accelerated approval to a full approval. Both companies will pursue additional international regulatory approvals for the R/R FL indication.

Data from the Phase 3 EPCORE FL-1 study will be presented at the Annual Meeting and Exposition of the American Society of Hematology (ASH) in December 2025.

About the EPCORE^® FL-1 Trial 
EPCORE FL-1 (NCT05409066) is a Phase 3 open-label randomized interventional trial to evaluate the safety and efficacy of epcoritamab plus rituximab and lenalidomide (R²) versus R² alone in patients with relapsed/refractory (R/R) follicular lymphoma (FL). Patients were randomized to receive EPKINLY in combination R² (n=243) or R² alone (n=245). Patients received EPKINLY in 28-day cycles for a total of 12 cycles or until disease progression or unacceptable toxicity, whichever occurred first. Efficacy was established based on the dual primary endpoints of progression free survival (PFS) and overall response rate (ORR) determined by Lugano 2014 criteria as assessed by Independent Review Committee (IRC). Additional efficacy outcome measures include complete response (CR) and duration of response (DOR).

EPKINLY® (epcoritamab-bysp) U.S. INDICATIONS AND IMPORTANT SAFETY INFORMATION

What is EPKINLY?
EPKINLY is a prescription medicine used to treat adults with:

• certain types of diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma that has come back (relapsed) or that did not respond (refractory), after 2 or more treatments.
  • EPKINLY for the treatment of DLBCL is approved based on patient response data. Studies are ongoing to confirm the clinical benefit of EPKINLY.
• follicular lymphoma (FL) that has come back or that did not respond to previous treatment, together with lenalidomide and rituximab
• follicular lymphoma (FL) that has come back or that did not respond after receiving 2 or more treatments.

It is not known if EPKINLY is safe and effective in children.

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 lead to death. 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.

People with follicular lymphoma (FL) may need to be hospitalized after receiving their first full dose of EPKINLY on Day 22 of Cycle 1 due to the risk of CRS.

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, feeling weak or generally unwell, or confusion.
• 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 and lymphopenia), 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.

The most common side effects of EPKINLY when used alone in DLBCL or high-grade B-cell lymphoma or FL include CRS, injection site reactions, tiredness, muscle and bone pain, fever, diarrhea, COVID-19, rash, and stomach-area (abdominal) pain. The most common severe abnormal laboratory test results with EPKINLY when used alone include decreased white blood cells, decreased red blood cells, and decreased platelets.

The most common side effects of EPKINLY when used together with lenalidomide and rituximab in FL include rash, upper respiratory tract infections, tiredness, injection site reactions, constipation, diarrhea, CRS, pneumonia, COVID-19, and fever. The most common severe abnormal laboratory test results with EPKINLY when used together with lenalidomide and rituximab include decreased white blood cells and decreased platelets.

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.

About EPKINLY^®  (epcoritamab-bysp)
EPKINLY^® (epcoritamab-bysp) is an IgG1-bispecific antibody created using Genmab's proprietary DuoBody^® technology and administered subcutaneously. Genmab's DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.^vi 

Epcoritamab (approved under the brand name EPKINLY in countries including the U.S. and Japan, and as TEPKINLY^® in the European Union) has received regulatory approval in certain lymphoma indications in more than 65 countries. Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies' oncology collaboration. The companies will share commercialization responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. Both companies will pursue additional international regulatory approvals for the R/R FL indication and additional approvals for the R/R DLBCL indication. 

Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes four additional ongoing Phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL compared to investigators choice immunochemotherapy (NCT04628494), a trial evaluating epcoritamab in combination with R-CHOP in adult patients with newly diagnosed DLBCL (NCT05578976), a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R²) compared to chemoimmunotherapy in patients with previously untreated FL (NCT06191744), and a trial evaluating epcoritamab in combination with lenalidomide compared to chemotherapy infusion in patients with R/R DLBCL (NCT06508658). The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit www.clinicaltrials.gov for more information.

About AbbVie in Oncology
AbbVie is committed to elevating standards of care and bringing transformative therapies to patients worldwide living with difficult-to-treat cancers. We are advancing a dynamic pipeline of investigational therapies across a range of cancer types in both blood cancers and solid tumors. We are focusing on creating targeted medicines that either impede the reproduction of cancer cells or enable their elimination. We achieve this through various, targeted treatment modalities and biology interventions, including small molecule therapeutics, antibody-drug conjugates (ADCs), immuno-oncology-based therapeutics, multispecific antibody and novel CAR-T platforms. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines.

Today, our expansive oncology portfolio comprises approved and investigational treatments for a wide range of blood cancers and solid tumors. We are evaluating more than 35 investigational medicines in multiple clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.

About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas including immunology, oncology, neuroscience and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.

AbbVie Forward-Looking Statements 
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry, the impact of global macroeconomic factors, such as economic downturns or uncertainty, international conflict, trade disputes and tariffs, and other uncertainties and risks associated with global business operations. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2024 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its Quarterly Reports on Form 10-Q and in other documents that AbbVie subsequently files with the Securities and Exchange Commission that update, supplement or supersede such information. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

Contacts:

Media: Anisha Bagchi Manix Email: anisha.manix@abbvie.com

Investors: Liz Shea  Email:  liz.shea@abbvie.com

ⁱ EPKINLY (epcoritamab-bysp) [package insert]. Copenhagen, Denmark: Genmab, 2025.
ⁱⁱ Lymphoma Research Foundation official website. https://lymphoma.org/aboutlymphoma/nhl/fl/. Accessed November 2025.
ⁱⁱⁱ Leukemia & Lymphoma Society. https://www.lls.org/research/follicular-lymphoma-fl. Accessed November 2025.
^iv Ghione P, Palomba ML, Ghesquieres H, et al. Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study. Haematologica. 2023;108(3):822-832. doi: 10.3324/haematol.2022.281421.
^v Al-Tourah AJ, Gill KK, Chhanabhai M, et al. Population-based analysis of incidence and outcome of transformed non-Hodgkin's lymphoma. J Clin Oncol. 2008 Nov 10;26(32):5165-9. doi: 10.1200/JCO.2008.16.0283. Epub 2008 Oct 6. PMID: 18838711.
^vi Engelberts PJ, et al. DuoBody-CD3xCD20 Induces Potent T-Cell-Mediated Killing of Malignant B Cells in Preclinical Models and Provides Opportunities for Subcutaneous Dosing. EBioMedicine. 2020;52:102625. doi: 10.1016/j.ebiom.2019.102625.

 

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SOURCE AbbVie

FAQ

What did AbbVie (ABBV) announce about EPKINLY on November 18, 2025?

The FDA approved EPKINLY + R2 for relapsed or refractory follicular lymphoma after ≥1 prior systemic therapy.

How effective was EPKINLY + R2 in the EPCORE FL-1 Phase 3 trial (ABBV)?

EPKINLY + R2 showed 89% ORR, 74% CR, and a 79% reduction in progression/death risk (HR 0.21).

What was the median progression-free survival for EPKINLY + R2 versus R2 in EPCORE FL-1?

Median PFS was not reached with EPKINLY + R2 versus 11.2 months for R2.

What are the key safety concerns for EPKINLY + R2 reported by AbbVie (ABBV)?

Common adverse reactions include rash, infections, fatigue, and CRS in 24%; there is a Boxed Warning for CRS and ICANS.

Is EPKINLY now fully approved for follicular lymphoma or conditionally approved?

With the confirmatory Phase 3 data, the FDA converted the prior accelerated approval to a full approval for this indication.