The impact of MRD and post-remission strategies on outcomes following dose-dense mini-hyper-CVD inotuzumab and blinatumomab in relapsed B-cell acute lymphoblastic leukemia.

Abstract

6516 Background: Advances in immunotherapy have improved outcomes for relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, the optimal sequence of immunotherapies remains undefined, particularly the role of chimeric antigen receptor (CAR) T-cell therapy in the era of sensitive assessment of measurable residual disease (MRD). Here, we provide an update of the phase II trial the dose dense mini-CVD with inotuzumab ozogamicin (InO) and blinatumomab (blina) regimen in R/R B-ALL. Methods: Adults (>18 years) with R/R Philadelphia (Ph) positive (+) or negative (-) B-ALL were treated with dose-dense mini-hyper-CVD with InO and blina. Cycles 1, 3, 5 consisted of mini-hyper-CVD, InO and blina; cycles 2, 4, 6 consisted of mini-methotrexate and ara-C, InO, and blina with Peg-G-CSF administered after each course. Patients (Pts) received 12 IT chemotherapy administrations and rituximab if CD20 positive. Pts with Ph+ ALL received a concomitant BCR::ABL1 tyrosine kinase inhibitor. MRD was assessed by flow cytometry (FC) and next-generation sequencing (NGS). Results: Between September 2021 and January 2026, 27 pts were enrolled (median age 42 years; range, 19–63). Three pts (11%) had Ph+ ALL, and among Ph- pts, 30% had Ph-like disease. Five pts (19%) had adverse risk cytogenetics and (24%) had a TP53 mutation. Twenty-four pts (89%) were in salvage 1. Three pts (11%) had previously undergone allogeneic stem cell transplant (SCT) and 9 (33%) had received blina. All pts achieved complete remission (CR) or CR with incomplete count recovery (CRi), including 22 (81%) CR. MRD negativity was achieved in 96% of pts by FCM and 95% by NGS; 80% and 44% achieved FCM and NGS MRD negativity, respectively, after the first cycle. With a median follow-up of 32 months, 11 pts (41%) proceeded to CAR T-cell consolidation, 5 (18%) to SCT, and 11 (41%) received no further consolidation. Among CAR T recipients, 70% were NGS MRD-negative prior to lymphodepletion. Post CAR T-cells infusion, 10/11 (91%) pts achieved/maintained NGS MRD negativity, while 1 (9%) pt had MRD below level of detection at last follow-up. The 2-year overall survival (OS) and event-free survival (EFS) rates for the entire cohort were 68% and 79%, respectively. The 2-year EFS rates for pts receiving CAR T-cell, ASCT, or no further consolidation were 81%, 80% and 50%, respectively, while the corresponding 2-year OS rates were 89%, 100%, and 55%. Conclusions: Dose-dense mini hyper-CVD combined with InO and blina induces high rates of deep NGS-MRD negative remission in patients with R/R B-ALL, allowing for consolidative strategies including CAR T-cell therapy, leading to favorable survival outcomes at a follow-up of almost 3 years. Clinical trial information: NCT01371630 .