The FDA has approved epcoritamab-bysp (Epkinly™, Genmab US, Inc.) for relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified. This approval includes high-grade B-cell lymphoma after two or more lines of systemic therapy and DLBCL arising from indolent lymphoma.
Why it matters: "Treatment regimens incorporating anti-CD20 monoclonal antibodies have become the standard of care for DLBCL and follicular lymphoma; however, intrinsic or acquired resistance will occur in the majority of patients, and therefore newer therapeutic interventions are needed," wrote the authors of the EPCORE NHL-1 trial (NCT03725037) trial, on which the approval was based, in their published evaluation of baseline samples. "Epcoritamab is a CD3-redirecting, CD20-targeting bispecific antibody that redirects patient tumor and peripheral T cells to lymphoma cells expressing CD20."
What they studied: Safety and efficacy were evaluated in the phase 1/2, open-label, single-arm, multicohort trial in which patients with relapsed/refractory DLBCL and high-grade B-cell lymphoma were given a dose-escalation treatment, 0.0128 to 60 mg, of epcoritamab in 28-day cycles to evaluate the appropriate dosage for phase 2 of the trial, which was set at 48 mg. The primary end point measured was overall response rate determined by Lugano 2014 criteria, as assessed by an independent review committee, with a secondary end point of duration of response.
What they found:
Adverse events: The most common adverse events in ≥20% of patients receiving epcoritamab were CRS, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea. The most common grade 3 to 4 laboratory abnormalities in ≥10% of patients receiving epcoritamab were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets.
What to know: The prescribing information for epcoritamab contains a Boxed Warning for serious or life-threatening cytokine release syndrome (CRS) and fatal immune cell–associated neurotoxicity syndrome (ICANS), as well as warning and precautions for infections and cytopenias. Among 157 patients who received the recommended dose of epcoritamab, 51% experienced CRS, including 37% grade 1, 17% grade 2, and 2.5% grade 3; 6% experienced ICANS, including 4.5% grade 1, 1.3% grade 2, and 0.6% grade 5; and 15% experienced serious infections. Patients should be hospitalized for 24 hours after the 48 mg dose on Cycle 1 Day 15 to be monitored for CRS and ICANS.
What's next: Further investigation of epcoritamab will be evaluated in ongoing phase 2 and 3 studies.
Conclusion: "Epcoritamab is a first-in-class, subcutaneously-administered, T-cell–engaging bispecific antibody that has shown good efficacy and safety in patients with relapsed or refractory large B-cell lymphoma who have received at least two prior systemic anti-lymphoma therapies, including those heaving pretreated and those with highly refractory disease," concluded Tycel Phillips, MD, Assistant Professor in the Division of Hematology and Oncology at the University of Michigan Rogel Cancer Center, and colleagues, in their publication of quality-of life results of the trial.
Instructions: The recommended dose of epcoritamab-bysp begins with step-up dosing in Cycle 1 as follows: 0.16 mg on Day 1, 0.8 mg on Day 8, and 48 mg on Day 15 and Day 22. Cycle 2 and 3 should consist of a fixed dosage of 48 mg weekly, followed by every other week in Cycles 4 through 9, and finally every four weeks on Day 1 of each cycle thereafter. Epcoritamab-bysp should be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.
For More Information
Blum J, Masters G, Chiu C, et al (2022). Deep peripheral T cell immune-profiling in relapsed/refractory non-Hodgkin lymphoma: evaluation of baseline samples from the epcoritamab Epcore NHL-1 trial. Blood (ASH Annual Meeting Abstracts), 40(suppl_1):6453-6454. DOI:10.1182/blood-2022-167189
Phillips T, Lugtenburg P, Kalsekar A, et al (2022). Improvements in lymphoma symptoms and health-related quality of life in patients with relapsed or refractory large B-cell lymphoma treated with subcutaneous epcoritamab (EPCORE NHL-1). Blood (ASH Annual Meeting Abstracts), 140(suppl_1):8022-8023. DOI:10.1182/blood-2022-159544
Hutchings M, Mous R, Clausen MR, et al (2021). Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet, 398(10306):1157-1169. DOI:10.1016/S0140-6736(21)00889-9
Clinicaltrials.gov (2023). First-in-human (FIH) trial in patients with relapsed, progressive, or refractory B-cell lymphoma (EPCORE™NHL-1). NLM identifier: NCT03625037.
Epkinly™ (epcoritamab-bysp) prescribing information (2023). Genmab US. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761324s000lbl.pdf
US Food and Drug Administration (2023). FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-diffuse-large-b-cell
Image credit: CoRus13. Licensed under CC BY-SA 4.0
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