Frontline and Maintenance Directions; Interpreting Real-World Data and Infection Prophylaxis

Dr. Lakshmi Nayak turns to the future role of BTK inhibitors in frontline and maintenance therapy. Dr. Motoo Nagane describes an ongoing Japanese trial evaluating BTK inhibition in the maintenance phase of newly diagnosed PCNSL and reflects on the limits of relapse monotherapy: rapid responses in many patients but a subset of non-responders and a relatively short duration of response, with durable remission in only a minority. He advocates more intensive, combination-based strategies incorporating chemotherapy and emerging options such as immunotherapy or bispecifics, while emphasizing the needs of elderly, unfit patients for whom transplantation and whole-brain radiotherapy are too toxic and targeted therapy may play a larger role. Dr. Nayak echoes the relevance of these points given that most patients are not transplant-eligible and that whole-brain radiation carries meaningful neurotoxicity. Dr. Christian Grommes then interprets the real-world data, agreeing that cardiac toxicity, liver toxicity, and bleeding have not been significant concerns with tirabrutinib. On infection, he recounts the early aspergillosis concern with ibrutinib and explains that his institution generally avoids fungal prophylaxis because it interferes with ibrutinib and potentially tirabrutinib levels, instead vigilantly screening heavily pretreated, chronically steroid-exposed patients with chest CT and imaging when symptoms arise.