Ibrutinib Origins and Tirabrutinib Tolerability in the PROSPECT Study

Dr. Christian Grommes revisits the early ibrutinib experience, when nearly every B-cell malignancy appeared responsive to BTK inhibition, and recalls the setback in non-CNS diffuse large B-cell lymphoma, where responses and progression-free survival were disappointing. He describes the decision to include both primary and secondary CNS lymphoma despite debate, and the notable finding that both responded better than systemic DLBCL, helping establish BTK inhibition in CNS lymphoma. Turning to the PROSPECT study, he reports that tirabrutinib produced responses similar to or better than the Japanese data with markedly better tolerability: less cardiotoxicity, no observed Aspergillus cases, and less rash than reported in Japan, with durable long-term responders and no significant cytopenias or cardiac toxicity even with prolonged exposure. He closes by contrasting the well-defined trial population with real-world, all-comers practice, underscoring why the ROSETTA real-world data, showing comparable response and even longer median progression-free survival, are so notable.