Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas.

Abstract

Simple SummaryTargeted therapies in children with hematological malignancies moderate the effects of cytotoxic therapy, thus improving survival rates. They have emerged over the last decade and are used in combination with or after the failure of conventional chemotherapy and as bridging therapy prior to hematopoietic stem cell transplantation (HSCT). Nowadays, there is a growing interest in their efficacy and safety in pediatric patients with refractory or relapsed disease. The compromised immune system, even prior to therapy, requires prompt monitoring and treatment. In children with hematological malignancies, targeted therapies are associated with a comparable incidence of infectious complications to adults. The exact impact of these agents that have different mechanisms of action and are used after conventional chemotherapy or HSCT is difficult to ascertain. Clinicians should be cautious of severe infections after the use of targeted therapies, especially when used in combination with chemotherapy.The aim of this review is to highlight mechanisms of immunosuppression for each agent, along with pooled analyses of infectious complications from the available medical literature. Rituximab confers no increase in grade ≥3 infectious risks, except in the case of patients with advanced-stage non-Hodgkin lymphoma. Gemtuzumab ozogamicin links with high rates of grade ≥3 infections which, however, are comparable with historical cohorts. Pembrolizumab exhibits a favorable safety profile in terms of severe infections. Despite high rates of hypogammaglobulinemia (HGG) with blinatumomab, low-grade ≥3 infection rates were observed, especially in the post-reinduction therapy of relapsed B-acute lymphoblastic leukemia. Imatinib and nilotinib are generally devoid of severe infectious complications, but dasatinib may slightly increase the risk of opportunistic infections. Data on crizotinib and pan-Trk inhibitors entrectinib and larotrectinib are limited. CAR T-cell therapy with tisagenlecleucel is associated with grade ≥3 infections in children and is linked with HGG and the emergence of immune-related adverse events. Off-label therapies inotuzumab ozogamicin, brentuximab vedotin, and venetoclax demonstrate low rates of treatment-related grade ≥3 infections, while the addition of bortezomib to standard chemotherapy in T-cell malignancies seems to decrease the infection risk during induction. Prophylaxis, immune reconstitution, and vaccinations for each targeted agent are discussed, along with comparisons to adult studies.