In 2023, a decade after granting Accelerated Approval to the first-in-class BTK inhibitor ibrutinib for the treatment of mantle cell lymphoma, the FDA requested this indication be withdrawn. Herein, we discuss the seemingly inconsistent results from the SHINE and TRIANGLE trials, which relate to the distinct patient populations of these trials, and posit that regulatory approaches should take these nuances into account.
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The research of E.R.S.C. and A.S.K. is funded by Arnold Ventures. The funders had no role in the design and conduct of the study, collection, analysis and interpretation of the data, preparation, review or approval of the manuscript, or decision to submit the manuscript for publication. The authors thank N. Mehta-Shah for discussions regarding romidepsin.
A.S.K. reports having served as an expert witness on behalf of the Leukemia and Lymphoma Society in litigation relating to royalties on venetoclax (2021–2022). E.R.S.C. and T.H. have no competing interests to declare.
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Cliff, E.R.S., Hilal, T. & Kesselheim, A.S. Complicated regulatory decision-making following inconsistent trial results: the issue with ibrutinib for mantle cell lymphoma. Nat Rev Clin Oncol (2023). https://doi.org/10.1038/s41571-023-00821-7