Dr Vose on Mitigating Epcoritamab-Associated CRS and Neurologic Toxicities in R/R DLBCL

Julie M. Vose, MD, MBA, division chief, Neumann M. and Mildred E. Harris Professor, physician, oncology and hematology, Division of Hematology and Oncology, University of Nebraska Medical Center, discusses the mitigation of treatment-related toxicities with epcoritamab-bysp (Epkinly) in an optimization cohort of adults with relapsed/refractory diffuse large B‑cell lymphoma (DLBCL) from the phase 1/2 EPCORE™ NHL-1 trial (NCT03625037).

On May 19, 2023, the FDA granted accelerated approval to epcoritamab for pretreated patients with relapsed or refractory DLBCL not otherwise specified. The decision was supported by findings from the dose expansion portion of EPCORE NHL, in which single-agent subcutaneous epcoritamab produced deep, durable responses with a manageable safety profile in this patient population.

Notably, cytokine release syndrome (CRS) events in the dose expansion portion of the trial were primarily low grade, and subcutaneous administration, step-up dosing, and premedication with prednisolone, were used to mitigate events. To further investigate whether mitigation strategies can reduce toxicities and improve outcomes with epcoritamab monotherapy, researchers created an optimization cohort of patients previously treated with 2 or more lines of systemic therapy, Vose begins.

Patients received subcutaneous epcoritamab in 28-day cycles: weekly for cycles 1 to 3, every 2 weeks for cycles 4 to 9, and every 4 weeks thereafter or until progressive disease or unacceptable toxicity occurred. Two step-up doses preceded 48-mg full doses, Vose adds.

To address CRS, cycle 1 of the optimization cohort mandated 15 mg of dexamethasone as premedication on days 1, 8, 15, and 22, with prophylaxis on days 2 to 4, 9 to 11, 16 to 18, and 23 to 25,* alongside diphenhydramine and acetaminophen on the same days. Hydration was strongly recommended, and antihypertensive medications were withheld for 24 hours before epcoritamab administration. Patients were advised to monitor their temperatures after the first 4 doses, with optional hospitalization and inpatient observation.