FITNESS STATUS AND TIME TO FIRST PROGRESSION IN ELDERLY PATIENTS WITH MANTLE CELL LYMPHOMA: RESULTS FROM THE “ELDERLY MANTLE-FIRST” STUDY

Mantle cell lymphoma (MCL) is an incurable disease. Elderly pa- tients represent the majority of cases, with heterogeneous but unsatis- factory outcomes. We aimed to confirm the prognostic impact of time to first progression of disease (early-POD ≤ 24 months versus late-POD > 24 months) in a multicenter cohort of elderly patients with MCL, and to assess the role of fitness status, defined by a simplified geriatric assess- ment (sGA). We collected a real-life series of 231 MCL patients aged ≥65 years, that experienced first relapse or were refractory to frontline non-intensive chemo-immunotherapy (CIT). We evaluated the safety and effectiveness of different second-line treatments, and compared Bruton Tyrosine Kinase inhibitors (BTKi) (124 patients) versus salvage CIT (65 patients). The 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 reports from the literature, possibly due to the median age of our cohort (77 years) and to the inferior fitness status (>50% unfit/frail). Early-POD patients showed a dismal prognosis, with a median PFS from second-line therapy (PFS-2) of 0.66 years ver- sus 1.47 years for late-POD cases (p-value 0.007), and a median overall survival from second-line therapy (OS-2) of 1.34 years versus 3.17 years (p-value 0.007) (Figure 1 A, B). Fitness status emerged as crucial prog- nostic parameter (Figure 1 C, D). Fit patients with late relapse had the best prognosis (3-year PFS-2 34%, OS-2 62%), whereas unfit/frail pa- tients showed quite similar outcomes regardless of time to POD. In con- clusion, in a real-life cohort of elderly patients with MCL, we confirmed the role of BTKi as standard salvage therapy and the prognostic impact of early-POD. Moreover, fitness status emerged as an essential prognos- tic tool, apparently stronger than time to POD, and should be incorpo- rated in future clinical trials.