Background: Older pts with DLBCL are increasing in the US and are most vulnerable to treatment related toxicities and mortality (TRM). Effective tools to predict and mitigate toxicity are essential in these pts. The RICOVER-60 trial implemented a “pre-phase” of vincristine and prednisone (Pred) to reduce disease symptoms and improve KPS, reporting decreased early TRM. This prospective pilot study in older DLBCL pts employs a pre-phase of Pred and rituximab (R) as part of a larger CGA validation study in NHL (n = 200; NCT01829958). Methods: Eligible pts (n = 30) had de novo DLBCL/tDLBCL, age ≥ 70 yrs or ≥ 60 yrs with KPS < 80%, and planned RCHOP-like therapy for 2+ cycles. CGA consisted of CARG and CRASH scores as largely self administered assessments. CGA was assessed at baseline, post pre-phase, with each cycle, and at end-of-therapy. Pre-phase included Pred 50-100mg x 5-10 days and R 375mg/m2 x1 day completed in the 14 days pre-RCHOP. The study is powered to show a 15% change in CGA risk score, with secondary endpoints of toxicity, TRM, PFS/OS. Results: Of 30 pts: median age 75 (range 65-85), female 59%, DLBCL 87%, Stage III/IV 60%, aaIPI high-int/high 57%, cell of origin GC/non-GC 55%/45%, median ki67 70% (range 60-90%). 97 % completed pre-phase and 2+ cycles of chemotherapy. Median followup is 6m (range 1-18m) with 28/30 pts alive. Impact of pre-phase: KPS median increased from 70% to 80% (p = .057)post pre-phase; Timed up-and-go was not significantly changed (p = .484), but 4/7 normalized post-pre-phase; Pre-phase therapy (n = 29) improved CGA risk scores compared to baseline ( p = .024). CGA predicted risk of G3+ toxicity was 65%(range 32-89%). Toxicity risk score reduced in 31% (9/29) pts, mean 16% risk reduction for G3+ toxicity. Focusing on early toxicity (C1-C3), actual non-heme grade 3+ events were 41% and heme G4+ events 16%. Hospitalization occurred in 37%. There was no reported TLS or early TRM (n = 30). 1 pt pursued hospice after pre-phase. Conclusions: A pre-phase intervention of Pred and R may mitigate early toxicity, resulting in improved KPS and CGA risk score, with no TLS or early TRM in this pilot. Clinical trial information: NCT01829958