605 | REFINING TREATMENT PARADIGMS FOR MANTLE CELL LYMPHOMA: A TAILORED APPROACH

Abstract

W. S. Kim, M. Al-Mansour, C. Cheah, A. Elghandour, E. Hawkes, H. Huang, B. Ko, D. Leão Cordeiro de Farias, Z. Li, S. Y. Ong, M. A. Pavlovsky, F. Perez-Zinzer, and Y. Song equally contributing author. Introduction: Advances in mantle cell lymphoma (MCL) treatments, including novel regimens and BTK inhibitors (BTKi), challenge the traditional role of autologous stem cell transplantation (ASCT) offering effective alternatives. Methods: This expert opinion reflects the insights of 14 specialists from AUS, ARG, BRA, CHN, EGY, MEX, SAU, SGP, KOR, and TWN, gathered through online discussion and an in-person meeting. Experts evaluated emerging MCL treatments, including BTKi, chemotherapy-free regimens, T-cell engagers (TCE), and CAR-T therapies. Results: ASCT Eligibility: Local guidelines vary, but patient fitness, organ function, and comorbidities (e.g., chronic kidney disease, poorly controlled diabetes) are key determinants. Genetic markers like TP53 mutation and Ki-67 indicate high risk, reducing the ASCT option. Most experts agree that ASCT’s role is diminishing due to emerging therapies. Recent data, including EA4151 and the TRIANGLE four-year follow-up, support this shift, signaling a major change in MCL treatment. First-line Therapy (1L): Bendamustine and rituximab (BR), with high-dose Ara-C for more aggressive cases, remain the standard of care for transplant-ineligible patients. Incorporating BTKi into 1L has shown improved outcomes, offering an effective ASCT-free option. Second-generation BTKi (e.g., acalabrutinib) significantly improves progression-free survival, when combined with BR in ineligible ASCT patients. Experts agree that using BTKi in 1L could lead to better outcomes compared to second-line (2L) use due to high attrition rates, with 40%–55% of patients unable to proceed to subsequent lines of therapy. Some experts prefer saving BTKi for 2L after BR or as an adjunct to BR. Accessibility and continuous BTKi therapy remain a challenge in some countries, but as an oral treatment, BTKi offers a more convenient option. Subsequent therapies: Chemotherapy-free options, including targeted therapies, CAR-T, and TCE, show potential for earlier-line MCL treatment, particularly for patients with poor fitness, comorbidities, or immunodeficiency. For fit patients, particularly those refractories to covalent BTKi therapy, CAR-T, and TCE therapies represent promising alternatives and may also be considered for BTKi-naïve or high-risk patients. While these therapies are anticipated to play a transformative role, concerns about limited clinical data, adverse events, and financial accessibility remain. Experts agree more robust evidence and studies to validate long-term benefits and refine patient selection are required before integrating these approaches into routine practice. Conclusions: Tailoring treatment strategies to individual patient profiles, considering genetic markers, comorbidities, and regional healthcare resources, is crucial. The evolving MCL landscape prioritizes personalized care, with targeted therapies like BTKi emerging as an effective 1L option for ineligible ASCT patients and a robust alternative to the ASCT regimen. Encore Abstract: EHA 2025 Keywords: non-Hodgkin No potential sources of conflict of interest.