CELL INTELLIGENCE · 肿瘤细胞治疗研究

PURPOSE OF REVIEW: Acute lymphoblastic leukemia (ALL) is a rare hematologic malignancy with a bimodal distribution of incidence in both pediatric/young adult and elderly patient populations. Despite the high complete remission rate, there is a high rate of relapse necessitating a need for therapy options in the relapsed/refractory setting. Given this, treatment paradigms for ALL have shifted towards targeted therapies and away from high-intensity chemotherapy.

The efficacy of inotuzumab ozogamicin (InO) in the relapsed/refractory setting for pediatric and adult populations has led to incorporation of this targeted therapy into frontline regimens. In this review, the role of InO in the frontline, measurable residual disease (MRD) positive and relapsed/refractory settings is highlighted.

RECENT FINDINGS: InO is a directed antibody-drug conjugate that binds to CD22 on the surface of leukemic blasts. The cell internalizes InO, prompting enzymatic cleavage in the lysosome that releases calicheamicin, inducing double-strand DNA breaks and causing apoptosis.

However, off-target effects can lead to severe adverse events such as hepatotoxicity, including veno-occlusive disease, and myelosuppression. Prior studies have supported its use in the relapsed or refractory treatment setting; however, newer studies incorporating InO in the frontline have shown promising results. Newer studies have also shown evidence of utilization of InO in specific sub-populations of B-cell ALL, including those with MRD-positive disease and Philadelphia-positive (Ph +) disease, and as bridging therapy with CAR T-cell therapy, and in the post-transplant maintenance setting.

This review evaluated the effectiveness of InO in clinical practice, associated adverse events, future directions in specific patient populations. Despite recent advancements, patients with B-cell ALL tend to have poorer outcomes, especially in the adult population. Future research and larger scale prospective studies are indicated to evaluate the efficacy of InO in different lines of therapy.