Demystifying changes with upfront therapy in Mantle Cell Lymphoma: Global clinician preparedness in the aftermath of educational interventions

Abstract Background: In recent decades, standard upfront therapy for mantle cell lymphoma (MCL) has featured chemoimmunotherapy (CIT) regimens of varying intensity followed by autologous transplant in eligible patients. Outcomes with CIT suggest that this strategy can be improved, including for early progressors and patients with high-risk features (Bond DA et al. Blood Adv. 2021;5:5179-5189; Eskelund CW et al. Blood. 2017;130:1903-1910). Covalent Bruton's tyrosine kinase inhibitors (BTKi) are among the standards of care in the 2L setting and have increasingly shown efficacy when combined with first-line (1L) CIT in autologous stem cell transplant (ASCT)-eligible and -ineligible patients, leading to regulatory changes and their inclusion in practice guidelines for frontline care (NCCN Clinical Practice Guidelines in Oncology. B-Cell Lymphomas. Version 2.2025; Eyre T et al. Br J Haematol. 2024;204:108-126). We assessed the impact of new evidence on 1L BTKi strategies in several educational interventions targeting clinicians in Europe and the United States. Methods: Four live in-person educational initiatives with tethered online enduring activities were developed to address these identified educational gaps. Data were collected from June 2023 to June 2025. Pre- and post-activity multiple-choice questions and practice-assessment polls measured changes in knowledge and skills. Additional questions assessed challenges and barriers to integrating BTKi into 1L settings. Results: In total, the educational activities engaged 5,486 physicians (3,273 learners from the European Union and 2,213 learners from the United States) who participated in person or virtually. After exposure to the education, learners demonstrated improvements in knowledge, including an increase of 32% in understanding of evidence supporting expanded roles for BTKi in the treatment of newly diagnosed MCL and a 37% increase in understanding of evidence supporting 1L chemo-free BTKi combinations (pre-activity n = 709, post-activity n = 455; P < .05). Learners reported increased conviction regarding clinical evidence supporting 1L BTKi regimens (26% of learners [n = 263] were convinced at baseline versus 84% [n = 206; P <.05] post activity). Furthermore, when presented with case-based questions, learners exposed to education were better prepared to integrate BTKi into 1L treatment, including use of more selective BTKi options (36% at baseline and 77% post activity) in ASCT and non-ASCT settings. Audience polling (N = 263) revealed that most learners (66%) identified the following as important unresolved questions related to the 1L use of BTKi in MCL: identification of candidates for BTKi/CIT combinations, when to defer ASCT in patients receiving upfront BTKi, safety of 1L BTKi combinations, and the role of chemo-free BTKi-based regimens. Conclusions: Serial, live in-person education with tethered online components has the ability to engage the treating community globally, improving understanding and application of clinically relevant data supporting the migration of BTKi into 1L management protocols. This improvement in skills was evident in different clinical settings (ie, for ASCT and non-ASCT settings). Collectively, these initiatives also uncovered areas of limited proficiency (eg, when to defer ASCT or integrate chemo-free strategies), highlighting the need for continued, skills-focused education.