Synthetic control arm from mixed clinical trials and real-world data from the LYSA group for untreated diffuse large B-cell lymphoma patients aged over 80 years: a bona fide strategy for innovative clinical trials

Patients over 80 years (≥80 y.o.) with newly diagnosed diffuse large B-cell lymphomas (DLBCL) are underrepresented in clinical trials (CT). Use of synthetic control arms (SCA) could help to build innovative comparative trials. With this analysis, we aim to demonstrate the clinical performance & use of such SCA. With data from both CT (LNH09-7B) and real-world (REALYSA), we built a mixed SCA composed of ≥80 y.o. patients with DLBCL in the first line of treatment. In order to display clinically meaningful results, we demonstrate how we can reproduce SENIOR results, a double-arm randomized CT, by switching the internal control arm with our newly built SCA. Patients between arms were balanced using a stabilized inverse probability of treatment weighting approach (sIPTW) based on propensity scores (PS), and the endpoint was overall survival (OS). All covariates included in PS were well balanced after weighting, and OS of Mixed SCA vs. SENIOR experimental arm were not statistically different, with a HR of 0.743 [0.494-1.118] (p = 0.1654). Use of SCA built only from real-world data (REALYSA) and sensitivity analyses using different missing data management methods didn't differ from the whole analysis. In newly diagnosed elderly DLBCL patients, the use of SCAs can mimic the control arm of an RCT and could be used to build comparative CT for elderly patients and come up with fast-innovative CTs.