Faculty, Staff and Student Publications

Publication Date

4-1-2024

Journal

Clinical Lymphoma, Myeloma & Leukemia

Abstract

Background: The combination of low-intensity chemotherapy and inotuzumab ozogamicin (INO), with sequential blinatumomab, is highly effective in older adults with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) and in relapsed or refractory B-cell ALL. Earlier, "dose-dense" administration of blinatumomab could lead to earlier and deeper measurable residual disease (MRD) responses and better outcomes.

Patients and methods: We performed a retrospective analysis of the safety and efficacy of a dose-dense regimen of mini-hyper-CVD (mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with mini-methotrexate and cytarabine), INO, and blinatumomab in patients with B-cell ALL.

Results: Twenty-one patients were treated (frontline, n = 9; MRD consolidation, n = 4; relapsed/refractory, n = 8). In the frontline cohort, all patients achieved CR/CRi and MRD negativity by flow cytometry at the end of cycle 1. Across the frontline and MRD consolidation cohorts, 10/11 patients (91%) achieved next-generation sequencing MRD negativity at a sensitivity of 10-6, including 6/10 evaluable patients (60%) who achieved next-generation sequencing MRD negativity after cycle 1. The CR/CRi rate in the relapsed/refractory cohort was 63%, and all responders achieved MRD negativity by flow cytometry at the end of cycle 1. The 1-year overall survival rate for the combined cohort of the frontline and MRD-positive patients was 83%. No new safety signals were observed with the dose-dense mini-hyper-CVD, INO, and blinatumomab regimen.

Conclusion: Dose-dense delivery of mini-hyper-CVD, INO, and blinatumomab was safe and resulted in rapid and deep MRD negativity in patients with B-cell ALL. This regimen is now being prospectively evaluated in both the frontline and relapsed/refractory settings.

Keywords

Humans, Aged, Inotuzumab Ozogamicin, Retrospective Studies, Philadelphia Chromosome, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Antibodies, Bispecific, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Cardiovascular Diseases, Antibody-drug conjugate, Bispecific antibody, CD19, CD22, Chemoimmunotherapy.

DOI

10.1016/j.clml.2023.12.016

PMID

38212207

PMCID

PMC11804792

PubMedCentral® Posted Date

4-1-2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

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