Background: Recent approvals and clinical trials have established covalent BTK inhibitors (BTKis), including ibrutinib, acalabrutinib, and zanubrutinib, as effective agents for the treatment of mantle cell lymphoma. Multiple BTKi-based regimens are recommended by experts and clinical guidelines in both the first-line and later-line settings. Additional approvals of the noncovalent BTKi pirtobrutinib and multiple CAR T-cell therapies have also advanced the management of patients who have progressed on covalent BTKi therapy. In light of these developments in treatment strategies for mantle cell lymphoma (MCL), this study compares trends in treatment choice among experts and healthcare professionals (HCPs) in an online treatment decision support tool.

Methods: An online decision support tool, developed with 5 US-based experts in MCL, was launched in April 2023 and updated in April 2025. The tool provided treatment recommendations for various clinical scenarios involving newly diagnosed (ND) or relapsed/refractory (R/R) MCL, incorporating factors such as age, fitness, previous therapies, and response duration. HCPs entered specific patient characteristics along with their intended treatment choice. The tool then displayed expert recommendations for that scenario, and HCPs were asked whether these recommendations influenced their treatment decision. HCP-entered data and expert recommendations were analyzed to identify common trends and divergence in current BTKi therapy use.

Results: The 2023 online tool was used by 119 HCPs who entered 148 patient scenarios, and the 2025 online tool was used by 69 HCPs who entered 96 patient scenarios. In 2023, for patients with ND MCL who had later-stage disease or were not eligible for radiation therapy (n = 75), 64% of expert-recommended treatments included BTKis, with the ECHO and TRIANGLE regimens representing 12% and 17% of recommendations, respectively. In 2025, 81% of expert recommendations were BTKi-based regimens, with ≥3 experts recommending a BTKi regimen in 66 of 67 unique ND case scenarios. The ECHO and TRIANGLE regimen each represented 28% to 29% of expert recommendations. In addition, 51% of recommendations for patients with 17p deletions or TP53 mutations consisted of the BOVen regimen. The percentage of HCPs who indicated that they were considering a BTKi-based regimen in the setting of ND MCL was 17% (13 of 75 ND cases) in 2023 and 66% (44 of 67 ND cases) in 2025. The use of both the ECHO and TRIANGLE regimens by HCPs increased from 5% and 4%, respectively, in 2023 to 19% for each in 2025. In 2025, 6% of HCPs considered the BOVen regimen for patients with TP53 mutation (n = 17).

In 2023 and 2025, approximately 50% of the HCP-entered patient cases for previously treated MCL had not received a BTKi (n = 48 and n = 18, respectively). For these scenarios, 94% and 98% of expert recommendations consisted of covalent BTKis in 2023 and 2025, respectively. HCPs selected covalent BTKis for 68% of cases in 2023 and 89% of cases in 2025. For patients with R/R MCL previously treated with a BTKi, CAR T-cell therapy represented 36% of expert recommendations in 2023 (23 scenarios) and 60% in 2025 (18 scenarios). By contrast, 4% and 11% of HCPs considered CAR T-cell therapy for these patients in 2023 and 2025, respectively.

For HCPs reporting on the tool's clinical impact (n = 96), 35% indicated expert recommendations changed their intended therapy, 41% stated their treatment plan matched the recommendations, 10% cited barriers to implementing recommendations, and 14% remained undecided on optimal treatment.

Conclusions:This analysis highlights the ongoing adoption of expert-recommended treatments into real-world clinical practice. Our data suggest that expert and HCP use of BTKi therapy in the ND MCL setting has increased in recent years. In R/R MCL, CAR T-cell therapy appears to be considered infrequently by HCPs. Barriers to implementation of expert recommendations warrant further investigation. Enhanced decision support tools and targeted educational initiatives could help increase the use of expert treatment recommendations and potentially improve patient outcomes.

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2025
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