Long-term outcomes with addition of inotuzumab ozogamicin to HCVAD and sequential blinatumomab in adults with newly diagnosed B-ALL.

6515 Background: Despite high remission rates with intensive chemotherapy and blinatumomab (blina) in newly diagnosed (ND) Philadelphia-negative (Ph-) B-ALL, relapse remains a major cause of treatment failure. Inotuzumab ozogamicin (InO) demonstrates efficacy in the relapsed setting and may improve outcomes in frontline. We report long-term results with 4.5 years of follow-up from the phase II study of HCVAD plus blina +/- InO for adults with ND Ph- B-ALL. Methods: Patients (pts) 18-59 years (yrs) with ND Ph- B-ALL received HCVAD alternating with high-dose methotrexate (MTX) and cytarabine (Ara-C) for up to 4 cycles, followed by 4 cycles of blina. Blina was initiated after 2 cycles of HCVAD for pts with high-risk features or persistent measurable residual disease (MRD) by multiparameter flow cytometry (FC). Starting with pt #39, InO was administered during the 2 MTX/Ara-C cycles and 2 blina cycles. Pts received 15 maintenance cycles with POMP and blina after every third cycle. Pts received 12 IT chemotherapies. Results: As of January 2025, 75 pts were treated (38 without InO cohort 1 and 37 with InO cohort 2). The median age was 33 yrs (range, 18–59); 37 for cohort 1 (18-59) and 25 (18-57) for cohort 2 (p=0.01). All other characteristics were similar. All pts (100%) achieved complete remission (CR). MRD-negativity by FC was achieved in 95% of pts at any time (66% at CR): 97% (76%) in cohort 1 and 94% (56%) in cohort 2. By next generation sequencing (NGS), 76% achieved MRD-negativity (26% at CR): 50% in cohort 1 and 79% in cohort 2. There were no early deaths. The median follow-up for cohorts 1 and 2 was 76 months (28-109) and 47 months (31-61), respectively. Of the 38 pts in cohort 1, 14 (37%) proceeded to allogeneic stem cell transplantation (SCT); of these, 11 (79%) remain alive in CR, 1 (7%) died in CR and 2 relapsed, 1 of which died. A total of 24 pts (63%) did not proceed to SCT; of these, 16 (67%) remain alive in CR, 3 (13%) died in CR, and 5 (20%) relapsed, 4 of which died. Of the 37 pts in cohort 2, 10 (27%) proceed to SCT; all alive in CR. A total of 27 pts (65%) did not proceed to SCT; 24 (89%) remain alive in CR (1 pt received CAR T-cell) and 3 (11%) relapsed, all of them alive in CR2). Median OS and event-free survival (EFS) have not been reached for either cohort. 4-year OS rates for the entire cohort, cohort 1 and cohort 2 are 91%, 82% and 100% (p=0.007), respectively, with 4-year EFS rates of 83%, 74%, and 91% (p=0.034), respectively. At 24 months, CIR was with InO vs without InO (8.1% vs 18.4%; p = 0.18). No deaths were observed in the InO group, whereas pts without InO had a 24-month cumulative incidence of death of 7.9% ( p = 0.08). Conclusions: Incorporation of InO into frontline HCVAD with sequential blina is associated with improved survival and durable remission in adults with ND Ph- B-ALL, supporting its role in the frontline setting. Confirmatory randomized trial comparing HCVAD-blina to HCVAD-blina-Ino is ongoing. Clinical trial information: NCI-2017-00596 .