Depletion of CD19-positive B-cells and dexamethasone premedication may result in immune suppression in patients with B-precursor acute lymphoblastic leukemia after consolidation treatment with blinatumomab

Treatment of patients with B-cell acute lymphoblastic leukemia (B-ALL) has benefited greatly from the introduction of different immunotherapy approaches targeting CD19 or CD22. In particular, when added to or when replacing some parts of chemotherapy treatment, blinatumomab, a bispecific T-cell engager which creates an immunological synapse between patient's CD3-expressing T lymphocytes and CD19-positive cells, including leukemia blasts, has shown unprecedented efficacy in preventing leukemia relapse/progression in both adults and children with either newly diagnosed or relapsed B-ALL. Despite the great anti-leukemia efficacy shown by blinatumomab, data obtained in large randomized studies in adults and children with newly diagnosed B-ALL have shown that the benefit of immunotherapy has, in part, been offset by an increased risk of infections, which can even occur long after completion of immunotherapy. Blinatumomab is also able to lyse normal B lymphocytes, and the resulting long-lasting, profound B-cell aplasia may lead to severe hypogammaglobulinemia, in turn increasing the incidence of infectious complications. Premedication with dexamethasone is widely used for mitigation of neurotoxicity and other systemic toxicities related to initial exposure to blinatumomab, but the dose usually employed does not derive from well-conducted studies aimed at identifying the recommended steroid dose. In addition, there is no robust evidence of a neuroprotective effect of Dexamethasone. This Spotlight Review aims to highlight the importance of monitoring immunoglobulin levels and to provide guidelines for initiation and continuation of immunoglobulin replacement therapy. In addition, we focus on need to conduct studies properly addressing the identification of optimal corticosteroid doses, regimens, and timing.