P373: updates from a phase ii trial of mini-hyper-cvd-inotuzumab with or without blinatumomab in older patients with newly diagnosed philadelphia chromosome (ph)-negative acute lymphoblastic leukemia

Background: The overall survival (OS) of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) has significantly improved with the introduction of targeted therapies, inotuzumab ozogamicin and blinatumomab. Combining these agents with low-dose chemotherapy in the frontline setting might improve outcomes. Aims: The aim of this analysis is to evaluate the combination of low-intensity chemotherapy mini-Hyper-CVD and inotuzumab ozogamicin, with or without blinatumomab, in older patients with newly diagnosed Ph-negative B-cell ALL. Methods: Adults ≥60 years with newly diagnosed Ph-negative B-cell ALL received mini-Hyper-CVD (mini-HCVD) for up to 8 cycles. Initially, inotuzumab ozogamicin was given at 1.3-1.8mg/m2 on Day 3 of Cycle 1 and 0.8-1.3mg/m2 on Day 3 of Cycles 2-4. Rituximab (if CD20+) and prophylactic intrathecal chemotherapy were given for the first 4 cycles. Responders received POMP maintenance for up to 3 years. Beginning with patient #50, inotuzumab ozogamicin was given in fractionated doses each cycle (0.6 mg/m2 on Day 2 and 0.3 mg/m2 on Day 8 of Cycle 1; 0.3 mg/m2 on Day 2 and 8 of Cycle 2-4) and 4 cycles of blinatumomab were given following 4 cycles of mini-HCVD plus inotuzumab. Maintenance was with 12 cycles of POMP and 4 cycles of blinatumomab (1 cycle of blinatumomab after 3 cycles of POMP). Results: 83 patients were treated, of whom 6 were in complete remission (CR) at enrollment (Figure 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 Cycle 1 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 patients (4%) developed veno-occlusive disease (VOD), 2 after subsequent ASCT. After a median follow-up of 65 months (range, 6-126), the 5-year 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-year OS for patients age 60-69 years 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. Summary/Conclusion: Favorable outcomes were observed in older patients with newly diagnosed Ph-negative ALL treated with mini-HCVD plus inotuzumab ozogamicin, with or without blinatumomab, with a 5-year OS of 48%. This regimen was well tolerated, with a low incidence of VOD and no early death observed.Keywords: Philadelphia chromosome, Phase II, Acute lymphoblastic leukemia