Mentor Name: Susan Rheingold

Blinatumomab, a CD19-directed bispecific T-cell engager that links CD3+ T cells to CD19+ B-lineage blasts, has fundamentally altered the treatment paradigm for pediatric B-cell acute lymphoblastic leukemia (B-ALL) and is now standard in frontline therapy. While its efficacy in improving event-free survival is well established, the real-world impact of blinatumomab on immune impacts and reconstitution, and infectious morbidity remains incompletely characterized. Blinatumomab-induced B-cell aplasia leading to secondary hypogammaglobulinemia may predispose patients to increased infectious complications during subsequent chemotherapy cycles compared to chemotherapy alone. Although grade =3 infections are captured in clinical trials, lower-grade viral and sinopulmonary infections are underreported despite their clinical relevance. These infections frequently result in cytopenias, hospital admissions, and chemotherapy delays or dose modifications, particularly during maintenance therapy. The cumulative impact of these interruptions on leukemia control and long-term outcomes remains unknown. Furthermore, secondary hypogammaglobulinemia and prolonged B-cell depletion raise concerns regarding loss of humoral immune memory and vaccine-derived protection. Data defining the depth and duration of immune suppression, kinetics of B-cell recovery, CD3/CD19 reconstitution, and vaccine titer persistence in pediatric patients are limited. Leveraging CHOP’s established immunotherapy surveillance infrastructure and growing real-world blinatumomab database, we will perform a retrospective cohort analysis of pediatric B-ALL patients treated with blinatumomab. Our primary focus will be analyzing the 30 patients who received blinatumomab in maintenance therapy with a secondary aim of looking at immune impacts of patients who received blinatumomab at any point during upfront therapy. Serial immunoglobulin levels, lymphocyte subset quantification, vaccine titers, IVIG utilization, and infectious events will be analyzed to characterize patterns of immune reconstitution and quantify infectious morbidity, including lower-grade infections. Data generated from this project will provide critical preliminary evidence to inform correlative immune reconstitution aims on cooperative group trials, including AALL1732, and will guide supportive care recommendations, vaccination strategies, and future trial designs incorporating additional cycles of blinatumomab during maintenance therapy. Ultimately, this work seeks to optimize the safety profile of blinatumomab while preserving its therapeutic benefit in pediatric B-ALL.