The role of time to first progression and fitness status in elderly patients with mantle cell lymphoma: results from the ELDERLY MANTLE-FIRST study

Mantle cell lymphoma (MCL) is an incurable disease. Elderly patients have heterogeneous but unsatisfactory outcomes. We aimed to confirm the prognostic impact of time to progression of disease (early-POD≤24 versus late-POD>24 months) in a multicenter cohort of elderly MCL patients, and to assess the role of fitness status, defined by a simplified geriatric assessment. We collected a real-life series of 231 MCL patients aged ≥65 years, in first relapse or refractory to frontline non-intensive chemo-immunotherapy (CIT). We evaluated safety and effectiveness of second-line treatments comparing Bruton Tyrosine Kinase inhibitors (BTKi, 124 patients) versus salvage CIT (65 patients). Median progression free survival (PFS) after BTKi was significantly longer compared to CIT (1.39 versus 0.98 years, p-value 0.037), though slightly inferior to previous studies, probably due to higher median age (77 years) and inferior fitness (>50% unfit/frail) of our cohort. Early-POD patients showed dismal prognosis, with median PFS from second-line therapy (PFS-2) 0.66 versus 1.47 years for late-POD (p-value 0.007), and median overall survival from second-line therapy (OS-2) 1.34 versus 3.17 years (p-value 0.007). Fitness status emerged as crucial prognostic parameter: late relapsed fit patients had the best prognosis (3-year PFS-2 34%, OS-2 62%), whereas unfit/frail patients showed similar outcomes regardless of time to POD. In conclusion, in a real-life cohort of elderly MCL patients we confirmed the role of BTKi as standard salvage therapy and the prognostic impact of early-POD. Moreover, fitness emerged as an essential prognostic tool, apparently stronger than time to POD, and should be incorporated in future trials.