C015 | PRE-PHASE TREATMENT WITH VITAMIN D SUPPLEMENTATION IN OLDER PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA: A RANDOMIZED TRAIL BY FONDAZIONE ITALIANA LINFOMI

Introduction: R-CHOP remains the standard treatment for fit elderly patients with DLBCL. In unfit and frail patients, it is either administered with reduced doses or modified by substituting conventional doxorubicin with its liposomal formulation. Recent data suggest that vitamin D (vitD) deficiency at diagnosis correlates with a worse prognosis in DLBCL. The Elderly Prognostic Index (EPI) is the first prognostic index specifically devised for older lymphoma patients. Methods: The hypothesis that maintaining normal vitD serum levels has a protective role against DLBCL progression provided the rationale for the PREVID trial. All patients received a prephase therapy with oral prednisone for 7 days before the first cycle of chemoimmunotherapy (ICT). Patients randomized to the experimental (exp) arm also associated prephase with vitD (cholecalciferol 25,000 U/day). Patients then received 6 cycles of ICT, and in the exp arm 25,000 U once weekly for the duration of ICT. All patients underwent sGA before starting treatment. The primary endpoint was 2-year progression-free survival (PFS). Results: A total of 342 patients were enrolled, of whom 314 were available for this first analysis (ref arm 156; exp arm 158). Induction treatments (R-CHOP 29%; R-mini-CHOP 10%; R-COMP 34%; R-mini-COMP 27%) were equally distributed among two arms. Overall, 224 patients (ref 105; exp 119) completed all 6 cycles of ICT, and 200 were assessed for response. VitD levels significantly increased in the exp arm after prephase (p <0.001) but remained unchanged in the ref arm throughout treatment (p=0.242). After a median follow-up of 16 months (range:1-42), PFS was evaluable in 307/314 patients (97.7%). The 2-year PFS was 65% (95% CI, 55-74) and 58% (95% CI, 47-68) in ref and exp arms, respectively (p= 0.260) (fig.1a). PFS stratified by baseline vitD levels showed a 2-year PFS of 68% (95% CI, 58-76) for patients with vitD >16 ng/mL and 54% (95% CI, 42-65) for those with vitD <16 ng/mL (p=0.0123) (fig.1b). The hazard ratio (HR) for high versus low EPI was 2.56 (95% CI, 1.34-4.91; p=0.004). Conclusions: This is the first randomized trial on vitD supplementation in older DLBCL patients. While low baseline vitD levels confirm an unfavorable prognostic role, as seen in previous studies, vitD supplementation did not improve outcomes. EPI is confirmed as a reliable prognostic index to identify high-risk elderly patients, even in a prospective study with homogeneously treated patients.