17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Abstract

Increasingly, novel agents are approved for the treatment of lymphoma by the US Food and Drug Administration (FDA) via accelerated approval and using single arm trials and surrogate efficacy measures, which leave uncertainty as to their clinical benefit. Methods: We reviewed the FDA website and [email protected] to identify approvals, conversions and withdrawals of novel agents for lymphoma from 2013 to 2022. From FDA approval summaries, we collected efficacy outcomes for pivotal trials, trial design, and type of approval (accelerated or regular). We extracted confirmatory trial characteristics and results from PubMed. Results: The FDA approved 19 novel drugs and 4 cellular therapies across 38 lymphoma indications. 25 (66%) indications received accelerated approval. All initial approvals were based on changes to surrogate measures: 7 (18%) on progression-free survival, 11 (29%) on overall response rate (ORR) plus duration of response, and 20 (53%) on ORR alone. 27 (71%) indications were approved based on single arm trials (22 accelerated, 5 regular). Just 6 (16%) indications have shown overall survival (OS) benefit in randomized trials. Of 25 accelerated approval indications, 4 (16%) have been converted, while 4 have been withdrawn due to toxicity (all Pi3K inhibitors). Conclusions: Many lymphoma therapies are FDA-approved based on single-arm trials and surrogate measures, while few have confirmed OS benefit. Timely randomized trials with meaningful clinical endpoints can help patients and clinicians choose among therapeutic options. The research was funded by: Arnold Ventures Keyword: Therapeutics and Clinical Trials in Lymphoma Conflicts of interests pertinent to the abstract. E. R. S. Cliff Research funding: Arnold Ventures W. B. Feldman Research funding: Arnold Ventures A. S. Kesselheim Research funding: Arnold Ventures