Bendamustine and the combination of fludarabine/cyclophosphamide are fully authorized chemotherapy agents in Switzerland for lymphoma treatment and currently used in routine clinical practice as lymphodepletion strategy before CAR-T immunotherapy, as supported by retrospective studies and clinical experience across multiple centers. None of the drugs described in this protocol are being used at unapproved doses, or in an investigational formulation. Both lymphodepletion regimens have a known safety profile and the risks and burdens imposed on participants do not exceed those encountered in routine CAR-T therapy management, as all procedures (including monitoring, supportive care, and follow-up assessments) align with standard clinical practice. Based on these assumptions, this protocol is designed to investigate the use of bendamustine as an alternative lymphodepletion therapy (which is a part of CAR-T immunotherapy protocol).
Diagnosis of large B-cell lymphoma (LBCL) with at least one line of previous treatment and indication for commercial CAR-T cell therapy as determined by the treating physician. This includes: Diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS) and all specific DLBCL subtypes, high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, transformed follicular lymphoma, and other transformed indolent B-cell lymphomas (including transformed marginal zone lymphoma and Richter's transformation). Patients with primary or secondary central nervous system (CNS) involvement are eligible.
Planned treatment with commercially available CAR-T cell product
Age ≥18 years
Ability to provide written informed consent
Administration of any other experimental drug within 5 half-lives or ≤ 4 weeks prior to lymphodepletion therapy starts.
Bendamustine 3 months before leukapheresis. After leukapheresis, bendamustine use is allowed as bridging therapy according to physician decision.
Previous administration of anti-CD19 CAR-T products within the last 12 months from lymphodepletion therapy start.
Known history of hypersensitivity to the active substance or any of the excipients found in the composition of bendamustine, fludarabine, or cyclophosphamide.