Background: The overall survival (OS) of patients (pts) with relapsed/refractory B-ALL has improved with the introduction of InO and Blina. Compared to conventional chemotherapy, the incorporation of these agents into the frontline setting of older pts with ALL may allow the use of less chemotherapy and potentially improve outcomes. Methods: Adults ≥60 yrs with newly diagnosed Ph-negative B-ALL received mini-Hyper-CVD (mini-HCVD) for up to 8 cycles. Initially, InO was given at 1.3-1.8mg/m² on Day (D) 3 of Cycle (C) 1 and 0.8-1.3mg/m² on D3 of C2-4. Rituximab (if CD20+) and prophylactic IT chemotherapy were given for the first 4 cycles. Responders received POMP maintenance for up to 3 yrs. Beginning with pt #50, InO was given in fractionated doses each cycle (0.6 mg/m² on D2 and 0.3 mg/m² on D8 of C1; 0.3 mg/m² on D2 and 8 of C2-4) and 4 cycles of Blina were given following 4 cycles of mini-HCVD plus InO. Maintenance was with 12 cycles of POMP and 4 cycles of Blina (1 cycle of Blina after 3 cycles of POMP). Results: 83 pts were treated, of whom 6 were in complete remission (CR) at enrollment(Table 1). Among 77 evaluable pts, 76 (99%) responded (CR, 90%). Among responders, the rates of MRD negativity by flow cytometry were 79% and 94% after C1 and overall, respectively. No early death was observed. Among 82 pts in remission, 11 (13%) relapsed, 4 (5%) underwent ASCT, 34 (41%) remain in ongoing continuous remission, 33 (41%) died in remission, of whom 9 died after developing MDS/AML. Three pts (4%) developed veno-occlusive disease, 2 after subsequent ASCT. After a median follow-up of 65 months (range, 6-126), the 5-yr continuous remission duration and OS rates were 78% and 48%, respectively. Age ≥70 and adverse cytogenetics were associated with worse outcomes. The inferior outcome in pts ≥70 yrs was primarily attributed to higher rates of death in CR. The 5-yr OS for pts age 60-69 yrs without adverse cytogenetics (n=40), age 60-69 with adverse cytogenetics (n=15), age ≥70 without adverse cytogenetics (n=24) and age ≥70 with adverse cytogenetics (n=4) were 72%, 27%, 38% and 0%, respectively. Conclusions: Favorable outcomes were observed in older pts with newly diagnosed Ph-negative ALL treated with mini-HCVD plus InO, with or without Blina. The 5-yr OS was 48%. Clinical trial information: NCT01371630.