Mantle Cell Lymphoma in Geriatric Patients: Biologic Risk Stratification, Fitness‐Adapted Strategies, and Unmet Needs

Marked by significant biological and clinical heterogeneity, mantle cell lymphoma (MCL) in older adults represents a growing clinical challenge, driven by an aging population, increasing burden of comorbidities, and reduced tolerance to intensive chemotherapy. This paper tackles contemporary therapeutic strategies for older and less fit patients with MCL. We conducted a structured review of the English literature using PubMed, Embase, and the Cochrane Library, including studies published between January 2000 and November 2025. Geriatric vulnerabilities are associated with increased toxicity and mortality and may preclude participation in clinical trials. As frontline, bendamustine-based chemoimmunotherapy followed by rituximab maintenance remains a feasible option. Second-generation Bruton tyrosine kinase inhibitors (BTKis) constitute valid options in both treatment-naïve and relapsed disease, being preferred in patients with high Ki-67 or when chemotherapy is contraindicated or refused. In TP53-mutated MCL, a second-generation BTKi combined with BCL2 inhibition ± anti-CD20 therapy appears promising, but larger trials are needed. In this age category, autologous stem cell transplantation and CAR-T therapy pose significant morbidity risks. Antibody-drug conjugates and bispecifics may offer additional options in later lines. Optimal management requires individualized, fitness-adapted strategies integrating biological risk and geriatric assessment. Continued development of well-tolerated regimens and rational sequencing is essential to improve outcomes.