Epcoritamab for Relapsed/Refractory B Cell Lymphoma - the Israeli Real-World Experience of a Compassionate Use Program

Introduction: Epcoritamab, a novel T-cell engager targeting CD20, has shown promising results in the treatment of various B cell malignancies. Clinical studies have shown high rates of complete responses and durable remissions, in patients with relapsed/refractory (R/R) B-cell malignancies. Furthermore, epcoritamab has displayed a manageable safety profile, with the most common adverse events (AEs) being mostly low-grade cytokine release syndrome (CRS) and infusion-related reactions. This study aims to evaluate the effectiveness, safety, and outcomes of epcoritamab treatment in R/R B-cell malignancies within a real-world cohort of patients. Methods: Patients' data was collected from medical records across 8 healthcare centers in Israel. Inclusion criteria were patients diagnosed with R/R B-cell malignancies who received epcoritamab as part of a compassionate use program. Demographic data, disease characteristics, previous treatment regimens, and AEs were recorded. Response to treatment was assessed using the Lugano criteria, while AEs were graded according to the Common Terminology Criteria for AEs (CTCAE) version 5.0. Statistical analysis was performed using R version 4.4.1. Kaplan-Meier survival analysis was employed to estimate progression-free survival (PFS), overall survival (OS). Results: The study included 23 patients, median age was 71.6 (range 19-89) and 13 (56%) patients were females. The median age at diagnosis was 67.1 years; median follow up period was 109.5 days. Fourteen (61%) patients had diffuse large B-cell lymphoma NOS, 3 (13%) had double or triple-hit lymphoma, 2 (8.7%) had primary mediastinal lymphoma, 1 (4.3%) had intravascular lymphoma and 3 (13 %) had follicular lymphoma. Most patients had IPI 3-4 at diagnosis (68%). Sixteen patients (72%) underwent CAR T-cell therapy and 2 (9%) underwent autologous stem cell transplantation prior to epcoritamab therapy. Epcoritamab was given at a median of 1.6 years (0.65-16.2) from diagnosis and after a median of 3 prior lines of therapy (2-6). Prior bispecific antibody treatment was given to one patient as 4th line therapy before epcoritamab. Ten patients had bulky disease (≥10cm) and 2 had bone marrow involvement at the time of treatment. All 23 patients received an initial epcoritamab dose of 0.16 mg. The subsequent 0.8 mg dose was administered to 22 patients, and 21 patients received the full 48mg treatment dose. CRS was reported in 12 patients (52%), 2 (8.7%) after each step-up dose and 8 (34%) after the first full dose. Five patients (22%) received tocilizumab, 4 of them after the 48mg dose. No cases of Immune Effector Cell-Associated Neurotoxicity Syndrome were reported. Five (21%) patients were hospitalized after the 0.16mg dose, 2 (8.7%) for CRS, 2 (8.7%) for infections and 1 (4.3%) for cytopenia. Eight (34%) patients were hospitalized after the 0.8mg dose, 2 (8.7%) for CRS, 5 (21%) for infections and 1 (4.3%) for cytopenias. All patients were hospitalized for observation after the full treatment dose. Grade 3-4 infections were reported in 7 (31%) patients during the treatment period, including neutropenic fever, pneumonia and COVID19 infections, and 1 case of fungal infection. The median number of epcoritamab cycles given was 3 (1-12). sixteen (69%) patients stopped the treatment, mainly due to progression (14/16, 87%). In the first imaging done in 13 patients after treatment initiation the overall response was 8/13 (61.5%) with CR in 5/13 (38.4%) patients. Eleven (68%) patients received another line of therapy after epcoritamab. The median OS and PFS was 6.3 and 3 months, respectively. The median duration of response (DOR) among responders was 2.3 months {95% CI 1.81, 5.12}, and among patients who achieved CR the median DOR was 6.4 months {1.5, 12.76}. Conclusions: Our findings indicate that the incidence of AEs aligns closely with the data reported in pivotal clinical trials. However, the observed response and survival rates in our cohort are somewhat inferior to those reported in these trials. Our data underscore the potential benefits of epcoritamab but also suggest that within thisa small cohort of heavily pretreated patients in a compassionate use program, the efficacy of epcoritamab for R/R B-cell malignancies may be lower than previously reported in controlled clinical .