Treatment Option for Adult Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Tahi Ahmadi, M.D., Ph.D.,
Executive Vice President & Chief Medical Officer, Head of Experimental Medicines, Genmab

Asud Khaliq,
Therapy Area Head, US Oncology Medical Affairs, AbbVie

This content is created and sponsored by Genmab and AbbVie, and is intended for US healthcare professional audience only.

Over the last three decades, research efforts in diffuse large B-cell lymphoma (DLBCL), a type of B-cell non-Hodgkin’s lymphoma (B-NHL)¹, have given way to significant progress in the diagnosis and treatment of this aggressive, fast-growing blood cancer. However, many people living with DLBCL, particularly those who face disease recurrence or do not respond to currently available standard-of-care therapies, continue to experience significant treatment challenges.²

Tahi Ahmadi, M.D., Ph.D., Executive Vice President & Chief Medical Officer, Head of Experimental Medicines, Genmab, and Asud Khaliq, Therapy Area Head, US Oncology Medical Affairs, AbbVie, discuss the current DLBCL treatment landscape and an effort as part of a collaboration between the two companies for people diagnosed with relapsed or refractory DLBCL.

Q. What is DLBCL? And how common is it?

Dr. Tahi Ahmadi, Genmab: Let’s start with non-Hodgkin's lymphoma (NHL), which represents not just one single disease, but rather a large group of blood cancers that come from abnormal lymphocytes, a type of white blood cell.¹ DLBCL comprises approximately 30 percent of all NHL cases¹ and is the most common subtype of NHL. There are approximately 30,400 new cases of DLBCL in the United States each year.³

Q. What is the current survival outlook if you are diagnosed with DLBCL in the United States?

Asud Khaliq, AbbVie: Currently, the five-year survival rate for DLBCL is 64.7 percent.² That’s an improvement from the five-year survival rate for DLBCL from 1975, which was 41.4 percent.² Many still face significant challenges, particularly as their disease advances and their treatment fails to respond. Among those with relapsed or refractory DLBCL, patients have a one-year survival rate of 28 percent post treatment.⁴

Q. What treatment approaches are currently available to support people with DLBCL? Are they currently meeting the needs of patients and caregivers when it comes to disease management?

Dr. Tahi Ahmadi, Genmab: There are several treatment options available for people diagnosed with DLBCL, including chemotherapy, radiation therapy, stem cell transplantation and drug therapy, including treatment options for people in the third-line setting, meaning those whose DLBCL relapses or becomes refractory after trying two other therapies.⁵

People living with relapsed or refractory DLBCL may require multiple courses of treatment and their life expectancy may decrease. This situation becomes especially challenging for people who have already undergone and failed two or more courses of therapy.

Bispecific antibodies, which are now commercially available, offer another third-line treatment option for people with relapsed/refractory DLBCL.⁶

Q. Bispecific antibodies are an area Genmab and AbbVie explored to address some of the treatment challenges of DLBCL in the third-line setting. Can you talk more about what bispecific antibodies are?

Asud Khaliq, AbbVie: Bispecific antibodies represent a novel class of therapies available for the treatment of cancer, particularly hematologic malignancies. Unlike typical antibodies that specifically target only one type of antigen in the body, bispecific antibodies target two antigens simultaneously.⁷ The ability to engage two different disease targets makes bispecific antibodies unique. The targets can be either two antigens on the cancer cell to block the cancer cell’s function, known as cross-linking, or one antigen on a cancer cell and one on an immune cell to help that immune cell target the cancer cell for destruction, a process called cell-bridging.⁸

Dr. Tahi Ahmadi, Genmab: This dual-targeted approach of bispecific antibodies had the potential to lead to positive outcomes when treating a complex and aggressive disease like DLBCL.^7,9 With Genmab’s DuoBody® platform, we can build on insights from the natural biology of antibodies. The platform generates stable bispecific IgG1 antibodies through controlled Fab-arm exchange. The DuoBody technology platform is capable of engineering bispecific antibodies that are stable and have pharmacokinetic properties similar to regular antibodies.¹⁰

Q. Your research in bispecific antibodies led to the U.S. Food and Drug Administration (FDA) approval of EPKINLY^TM (epcoritamab-bysp). What was EPKINLY approved for?

Dr. Tahi Ahmadi, Genmab: On May 19, 2023, we received FDA approval of EPKINLY, the first and only subcutaneous bispecific antibody for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma (HGBL) after two or more lines of systemic therapy.¹¹ This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).¹¹

Because EPKINLY works with the immune system, it can cause serious side effects, including Cytokine release syndrome (CRS), Immune effector cell–associated neurotoxicity syndrome (ICANS), Infections, Cytopenias, and Embryo-Fetal Toxicity.¹¹ Please see additional Important Safety Information, including Boxed Warnings for CRS and ICANS, below.

Q. Where can people go for more information?

Asud Khaliq, AbbVie: Together with Genmab, we are committed to continue to explore the therapeutic potential of EPKINLY for patients.

Through our collaboration, Genmab and AbbVie will continue to study other areas that may benefit from this product.

To learn more about EPKINLY, please visit www.epkinlyhcp.com.

IMPORTANT SAFETY INFORMATION
BOXED WARNINGS

• Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving EPKINLY. Initiate treatment with the EPKINLY step-up dosing schedule to reduce the incidence and severity of CRS. Withhold EPKINLY until CRS resolves or permanently discontinue based on severity.
• Immune effector cell–associated neurotoxicity syndrome (ICANS), including life-threatening and fatal reactions, can occur with EPKINLY. Monitor patients for neurological signs or symptoms of ICANS during treatment. Withhold EPKINLY until ICANS resolves or permanently discontinue based on severity.

CRS

• CRS occurred in 51% of patients in the clinical trial (37% grade 1, 17% grade 2, and 2.5% grade 3) and recurred in 16% of patients. Most events (92%) occurred during cycle 1, with 61% occurring after the 48 mg dose in cycle 1, day 15. In patients who experienced CRS, the signs and symptoms included pyrexia, hypotension, hypoxia, dyspnea, chills, and tachycardia. Concurrent neurological adverse reactions associated with CRS occurred in 2.5% of patients and included headache, confusional state, tremors, dizziness, and ataxia.
• Administer pretreatment medications to reduce the risk of CRS. Following administration of the first 48 mg dose, patients should be hospitalized for 24 hours.
• Monitor patients for potential CRS. At the first signs or symptoms of CRS, manage per current practice guidelines and administer supportive care as appropriate.

ICANS

• ICANS occurred in 6% of patients in the clinical trial (4.5% grade 1, 1.3% grade 2, 0.6% fatal). Of the 10 ICANS events, 9 occurred in cycle 1 of treatment. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical manifestations of ICANS included, but were not limited to, confusional state, lethargy, tremor, dysgraphia, aphasia, and non-convulsive status epilepticus.
• Monitor patients for potential ICANS. At the first signs or symptoms of ICANS, manage per current practice guidelines and administer supportive care as appropriate.

Infections

• EPKINLY can cause serious and fatal infections. In the clinical trial, serious infections, including opportunistic infections, were reported in 15% of patients treated with EPKINLY at the recommended dose (14% grade 3 or 4, 1.3% fatal).
• Monitor patients for signs and symptoms of infection prior to and during treatment and treat appropriately. Avoid administration in patients with active infections. Withhold or consider permanent discontinuation of EPKINLY based on severity. Prior to starting EPKINLY, provide Pneumocystis jirovecii pneumonia (PJP) prophylaxis and consider prophylaxis against herpes virus.

Cytopenias

• EPKINLY can cause serious or severe cytopenias. In the clinical trial, grade 3 or 4 events occurred in 32% (neutropenia), 12% (anemia), and 12% (thrombocytopenia) of patients. Febrile neutropenia occurred in 2.5%.
• Monitor complete blood counts throughout treatment. Based on severity of cytopenias, temporarily withhold or permanently discontinue EPKINLY. Consider prophylactic granulocyte colony-stimulating factor administration as applicable.

Embryo-Fetal Toxicity

• EPKINLY may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with EPKINLY and for 4 months after the last dose. Verify pregnancy status in females of reproductive potential prior to initiating EPKINLY.

Adverse Reactions

• Most common (≥20%) adverse reactions were CRS, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea. Most common grade 3 to 4 laboratory abnormalities (≥10%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.

Lactation

• Advise women not to breastfeed during treatment and for 4 months after the last dose of EPKINLY.

Please see the full Prescribing Information, including Boxed Warnings.

¹ Sehn LH, Salles G. Diffuse Large B-Cell Lymphoma. Longo DL, ed. N Engl J Med. 2021;384(9):842-858. doi:10.1056/NEJMra2027612.

² National Cancer Institute. Cancer Stat Facts: NHL – Diffuse Large B-Cell Lymphoma (DLBCL). Published online 2023. Accessed Aug. 10, 2023. https://seer.cancer.gov/statfacts/html/dlbcl.html.

³ Kanas G, Ge W, Quek RGW, et al. Leukemia & Lymphoma. 2022;63(1):54-63.

⁴ Liu Y, Barta SK. Diffuse large B-cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment. Am J Hematol. 2019;94(5):604-616.

⁵ Understanding Lymphoma: Non-Hodgkin Lymphoma (Lymphoid Neoplasms). Lymphoma Research Foundation. https://lymphoma.org/wp-content/uploads/2021/12/LRF_Non_Hodgkin_Lymphoma_Factsheet.pdf. Accessed May 5, 2023.

⁶ Zelenetz AD, Gordon LI, Abramson JS, et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) B-Cell Lymphomas Version 5.2023.

⁷ Lymphoma Research Foundation. Understanding Lymphoma and Bispecific Antibodies. Published online 2022. Accessed May 5, 2023. https://lymphoma.org/wp-content/uploads/2023/01/LRF_Dec-2022-Fact-Sheet-Layout_Bispecific-Antibodies.pdf.

⁸ Wu, Y., Yi, M., Zhu, S. et al. Exp Hematol Oncol. 2021;10(1):56.

⁹ Fan G, Wang Z, Hao M, Li J. J Hematol Oncol. 2015;8:130.

¹⁰ Labrijn AF et al. Proc Natl Acad Sci USA. 2013;110(13):5145-5150.

¹¹ EPKINLY [package insert].

12/2023 COM-US-EPK-0000369