Navigating B-ALL in the Era of Blinatumomab.

Abstract

Blinatumomab has rapidly emerged as a cornerstone in the treatment of B-cell ALL (B-ALL) across age and risk groups. Initially approved for minimal residual disease (MRD)-positive adult B-ALL in 2018, its indications have since expanded after pivotal trials demonstrating significant efficacy. The BLAST and E1910 trials highlighted the benefit of blinatumomab in adults in MRD-positive and MRD-negative remission, respectively, with notable improvements in overall survival and relapse-free survival. In pediatric populations, studies such as the AALL1731 and a landmark trial in infants with KMT2A-rearranged B-ALL demonstrated striking reductions in relapse when blinatumomab was added to standard regimens. Similarly, in Philadelphia chromosome-positive B-ALL, blinatumomab-based regimens have enabled chemotherapy minimization while achieving durable remissions. Despite these advances, the rapid integration of blinatumomab into standard care poses challenges related to administration, toxicity management, and equitable access. Variability in inpatient observation durations, infusion bag sizes, home health availability, and handling of infusion-related complications underscore the need for standardized delivery models. Additionally, low-grade and long-term toxicities-such as neurotoxicity, cytokine release syndrome, and hypogammaglobulinemia-remain undercharacterized. Looking forward, research is focusing on optimizing the use of blinatumomab, including its integration into reduced-intensity or chemotherapy-free regimens, alternative dosing schedules, and subcutaneous administration. As clinical use expands, emphasis must shift toward developing equitable, patient-centered delivery strategies and understanding the full spectrum of toxicities to ensure optimal and accessible care for all patients with B-ALL.