Clinical trial access after CAR T-cell therapy failure in relapsed/refractory large B-cell lymphoma

More than half of patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL) experience progression after chimeric antigen receptor (CAR) T-cell therapy, and subsequent treatment options remain limited with poor outcomes. Despite the need for effective therapies in this setting, post-CAR T clinical trial enrolment is low. We conducted a single-centre study of patients with r/r LBCL who progressed after CAR T-cell therapy between January 2018 and September 2023 to describe the practice patterns and identify factors associated with clinical trial participation. Patient, disease and clinical characteristics were analysed across screening, enrolment and treatment phases. Among 166 patients who progressed after CAR T-cell therapy, 39% were screened, 23% enrolled and 22% ultimately received trial treatment. High-risk clinical features, including eastern cooperative oncology group (ECOG) performance status ≥2, stage IV disease, high-risk International Prognostic Index, incomplete response to CAR T-cell therapy and severe cytokine release syndrome, were associated with non-participation. Using the eligibility criteria of pivotal trials that led to FDA approval of novel agents, only 14%-36% of patients who had relapsed disease after CAR T-cell therapy were eligible for these trials. The study highlights the unmet need to develop trials that accommodate high-risk populations to reduce barriers to trial participation following CAR T-cell therapy failure.