The dose-dense mini-hyper-CVD, inotuzumab ozogamicin (INO), and blinatumomab regimen showed safety and induced swift and profound measurable residual disease (MRD) negativity in patients with B-cell acute lymphoblastic leukemia (ALL), with a 1-year overall survival rate of 83%.

The following is a summary of “Dose-Dense Mini-Hyper-CVD, Inotuzumab Ozogamicin and Blinatumomab Achieves Rapid MRD-Negativity in Philadelphia Chromosome-Negative B-cell Acute Lymphoblastic Leukemia: Dose-dense mini-Hyper-CVD, inotuzumab ozogamicin and blinatumomab,” published in the December 2023 issue of Hematology by Short et al.

In the context of newly diagnosed B-cell acute lymphoblastic leukemia (ALL) in older adults and relapsed or refractory B-cell ALL, a regimen incorporating low-intensity chemotherapy coupled with inotuzumab ozogamicin (INO) and sequential blinatumomab has demonstrated notable efficacy. Exploring an earlier and more frequent administration schedule of blinatumomab, referred to as “dose-dense,” holds promise for attaining swifter and more profound measurable residual disease (MRD) responses, potentially enhancing overall outcomes.

A retrospective analysis was conducted to assess the safety and effectiveness of a dose-dense treatment protocol comprising mini-hyper-CVD (mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with mini-methotrexate and cytarabine), INO, and blinatumomab among patients diagnosed with B-cell ALL.

Twenty-one patients underwent this treatment, comprising nine in the frontline group, four in MRD consolidation, and eight in the relapsed/refractory category. In the frontline cohort, all patients achieved complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) and MRD negativity via flow cytometry after cycle 1. Collectively, across frontline and MRD consolidation groups, 10 out of 11 patients (91%) achieved next-generation sequencing (NGS) MRD negativity at a sensitivity of 10^-6, with six out of ten evaluable patients (60%) attaining NGS MRD negativity after cycle 1. 

The relapsed/refractory cohort exhibited a 63% CR/CRi rate, with all responders achieving MRD negativity via flow cytometry at the end of cycle 1. The 1-year overall survival rate for the combined frontline and MRD-positive patients was 83%. No new safety concerns were identified while administering the dose-dense mini-hyper-CVD, INO, and blinatumomab regimen.

The dose-dense delivery of mini-hyper-CVD, INO, and blinatumomab demonstrated safety and elicited rapid and profound MRD negativity in B-cell ALL patients. This regimen is currently under prospective evaluation in both frontline and relapsed/refractory settings to further validate its efficacy and safety.

Source: sciencedirect.com/science/article/abs/pii/S2152265023022164