It's "Blin" a Long Time Coming: The Rise of Blinatumomab in Philadelphia Chromosome-Negative Acute Lymphoblastic...

Blinatumomab is a bispecific T-cell engager that has recently transformed front-line treatment for many patients with Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (B-ALL). It was originally studied in relapsed/refractory disease, then moved to targeting measurable residual disease (MRD), and has since been shown to improve outcomes for almost every age group when added to consolidation chemotherapy. The evidence supporting blinatumomab is most robust in adult and standard-risk pediatric age groups, but its benefit in adolescents and young adults and high-risk pediatric patients is not yet understood. Clinical application becomes more complex when blinatumomab is incorporated into consolidation therapy within treatment protocols that were not originally designed to include it, raising questions about optimal integration in these settings. Furthermore, critical patient populations, such as those with high-risk disease features, MRD-positivity, relapsed disease, and/or plans for allogeneic hematopoietic cell transplant may require even more nuanced approaches to administration. While MRD is not a prerequisite for blinatumomab use, it remains an essential marker for disease monitoring, informs treatment timing, and continues to evolve with increasingly sensitive detection methods. This review summarizes the history of and more recent developments in MRD prognostication and how this relates to therapy decisions especially in the era of blinatumomab. It then discusses the pivotal trials on blinatumomab in both MRD-positive and MRD-negative Ph-negative B-ALL across all age groups and offers possible approaches to integrating blinatumomab in regimens and patient populations not currently addressed in the literature.