7577 Background: R-CHOP is the standard first-line treatment for pts with DLBCL; however, some pts are poor candidates due to general debility, cardiac disease, or other medical problems. Maintenance R is not effective after full course R-CHOP chemotherapy for DLBCL (ECOG 4494), but improves outcome following CHOP alone. In this phase II trial, we evaluated short course R/chemotherapy, followed by maintenance R, in pts who were not candidates for full-course R-CHOP. Methods: Eligibility: previously untreated DLBCL; stage II-IV; ECOG PS 0–2; age ≥ 70 years or poor CHOP candidate; adequate kidney, liver, bone marrow function; no HIV infection; informed consent. Pts received 3 courses of R-CNOP (cyclophosphamide 500mg/m2, mitoxantrone 10mg/m2, vincristine 1.0mg/m2, prednisone 80mg PO days 1–5, rituximab 375mg/m2) followed by pegfilgrastim 6mg sq day 2, at 21-day intervals. Mitoxantrone was omitted for pts with EF < 40%. Pts with response/stable disease after chemotherapy began maintenance R (375mg/m2 weekly × 4 doses, administered at 6-month intervals × 4 courses). Results: 31 pts entered this trial between 5/03 and 11/05. Clinical characteristics: median age, 78 years; ECOG PS 2, 45%; IPI 3–5, 79%. 27 pts (87%) have completed short course R-chemotherapy; 20 pts (65%) are currently receiving maintenance R. After completion of R-chemotherapy, 17 pts (63%) had responses (9 CR/CRu, 8 PR); 10 pts had stable disease/minor response. After median 16 month follow-up, 29 of 31 pts (94%) are progression-free; actuarial 2-year PFS is 90%. The 2-year overall survival is 74%. 4 pts have died (progressive lymphoma 2, intercurrent illnesses 2). Grade 3/4 toxicities: neutropenia 38%, other toxicities < 10%, no treatment-related deaths. Conclusions: Short-course R-chemotherapy followed by maintenance R was active and well tolerated in a group of elderly, poor prognosis pts with DLBCL. In spite of modest CR/CRu rate; the 90% 2-year PFS suggests a role for maintenance R. If these findings persist with further followup, this approach is worthy of further study in this patient group. [Table: see text]