Defining lines of therapy in haematological malignancies: a proposed systematic and comprehensive framework from the...

The therapeutic landscape of hematological malignancies has been transformed by targeted therapies, immunotherapy, and cellular therapies, leading to more complex and prolonged clinical courses. Currently, there is substantial variability in how "lines of therapy" (LoT) are defined and recorded, which hinders research and data harmonization. To address this, the EBMT Practice Harmonisation and Guidelines Committee has developed a standardized framework for LoT across acute leukemias, lymphomas, and multiple myeloma. A LoT is defined as a coherent therapeutic episode aimed at achieving or maintaining disease control, comprising one or more systemic treatment phases such as induction, consolidation, or maintenance, administered in the absence of disease progression, treatment failure, or major toxicity. A new LoT is assigned at documented progression, relapse, or primary refractory disease, and the introduction of an agent from a distinct therapeutic class to deepen response also constitutes a new line, whereas dose adjustments, schedule changes, or planned omissions to manage toxicity do not create a new LoT. Bridging therapies administered prior to cellular therapy, including CAR-T or transplantation, are considered part of the same LoT as the definitive treatment. This initiative aims to enhance methodological rigor, improve clarity in treatment reporting, and support evidence-based decision-making in precision hematology.