Yasmin H. Karimi, MD, on Large B-Cell Lymphoma: Follow-up on Subcutaneous Epcoritamab Monotherapy

EPCORE NHL-1 was a phase 2 trial evaluating Epcoritamab, a CD20, CD3-bispecific antibody in the treatment of relapsed refractory large cell lymphoma in the second line and beyond setting. In this poster, we presented longer term follow-up results, MRD results, as well as results from the optimization cohort. In the study, patients with relapsed refractory disease were enrolled and treated with Epcoritamab step-up dosing with full dose given on cycle 1, day 15. In the optimization cohort, the dosing schema remained the same. However, CRS prophylaxis was 15 milligrams, dexamethasone, and 500 milliliters of hydration. In the optimization cohort, hospitalization for CRS monitoring after full dose treatment was not required. 157 patients with large B-cell lymphoma were treated in the expansion cohort. The median age was 68 years, and patients had a median of three prior lines of treatment. This was a heavily pretreated patient population with 39% of patients having received a prior CAR-T and 83% refractory to the last line of treatment. The overall response rate in the study was 59% with 41% experiencing a complete response. A median follow-up time of 31 months. The median duration of CR has not yet been reached. An estimated 54% of complete responders remained in CR at 30 months. In patients in complete response, 80% of patients achieved MRD negativity at cycle 3 and 92% of patients experienced MRD negativity at any time point as assessed by clonoSEQ MRD. The most common treatment emergent adverse events were cytokine release syndrome, occurring at 51% of patients, fatigue, fever, neutropenia, diarrhea, nausea, anemia, and infections. There were 29% of patients that had a grade three or higher serious infection, and 10% discontinued therapy due to infection. As this trial was conducted during the COVID-19 pandemic and the omicron variant, there were 32 cases of COVID and nine deaths due to COVID. In the optimization cohort, the uniform use of dexamethasone and hydration, the incidents and severity of CRS occurred in about 37% of patients, and with the majority being low grade. Most CRS occurred after the first full dose of treatment and CRS events all resolved. Hospitalization was not mandatory and was at the discretion of the investigator. 60% of patients received outpatient therapy and only one patient required subsequent inpatient admission. After outpatient treatment, the remaining CRS events were managed without hospitalization. In summary, with over 2.5 years of follow-up of single agent Epcoritamab in relapse refractory large cell lymphoma, including high risk patient populations with prior CAR-T and primary refractory disease, the data continues to show ongoing durable responses in patients who achieve a CR and 62% of patients remain in CR at two years. In the optimization cohort data, in addition to another abstract printed in ash with outpatient Epcoritamab lends support to the safety of fully outpatient administration.