Mature T-cell lymphomas are a rare, aggressive group of blood cancers. With disease progression after receiving initial standard chemotherapy, there are only a few unique drug classes available for subsequent treatment, and there is no universally accepted standard of care for how to use them. Patients often cycle through different agents one after another, which are chosen based on small studies and limited available data. We used a rigorous study design with PETAL’s global dataset alongside three independent methods to examine each possible sequence of therapies, finding a survival benefit to using certain drugs earlier before others. This helps us use our available drugs more effectively and helps create a treatment framework that clinicians can use.