B-cell Enrollment Efficiency Program (BEEP): Streamlining accrual to early-phase lymphoma trials at a single center.

Abstract

e19084 Background: Enrolling patients with lymphoma into clinical trials is challenging due to stringent organ function eligibility criteria (Khurana A, 2021). This challenge is exacerbated by therapy-related CD20 antigen loss in heavily treated relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) patients. To streamline accrual to phase 1 and 1b trials we developed BEEP, an inaugural system tailored to optimize enrollment of extensively treated R/R B-NHL patients. Our initial experience is reported here. Methods: Eligible R/R B-NHL adult patients were nominated into BEEP by their primary oncologist for trial screening. Individual patients were pre-screened for each of the 10 active first-in-human studies in BEEP, and real-time feedback was provided to the primary oncologist. Patient status was updated regularly until a patient was enrolled in a trial, initiated another line of therapy, or died. Results: A total of 47 patients with R/R B-NHL were enrolled into BEEP between 05/01/2025 and 12/31/2025. Cohort median age was 63 years (range 27-84), with an 85% male predominance, 74% white racial composition, and a median of 5 prior lines (range 3-12) of systemic therapy. Histologic diagnoses were notable for 27 large B-cell lymphoma patients (13 DLBCL, 11 transformed indolent NHL, 3 Richter’s transformation), 19 low-grade lymphoma patients (9 low-grade follicular, 4 CLL, 3 mantle cell, 2 marginal zone, 1 Waldenström macroglobulinemia) and 1 accelerated CLL patient. Therapy-related antigen loss was observed in 17 patients (14 CD20-negative only, and 3 CD20/CD19 dual-negative). Of the 47 BEEP patients, 10 enrolled in clinical trials (8 in BEEP, 1 internal non-BEEP trial, and 1 external trial), 25 urgently initiated another line of therapy, and 12 remained on their pre-BEEP treatment waiting for a trial. A total of 6 patients died before trial enrollment (3 while waiting for a trial and 3 after starting another line of therapy). Universal exclusion from BEEP trials was observed in 8 patients (4 with active CNS involvement, 2 with renal insufficiency, 1 with CD20 loss/hepatic dysfunction, and 1 with CD20 loss/GVHD). A lack of available slots was the main reason screen-eligible patients were awaiting enrollment. Conclusions: Enrolling R/R B-NHL patients into phase I clinical trials remains an ongoing challenge. Our BEEP experience confirmed the unmet need in trials for patients with secondary CNS involvement, CD20 antigen loss, and limited organ function. Dynamic slot availability remains the biggest impediment to enrolling screen-eligible patients. Future phase 1 trials will need to adopt designs enabling continuous accrual without complete dose-limiting toxicity data, explore CD20/CD19-independent targeted agents, and reassess restrictive organ function eligibility criteria.