Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas

Abstract

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.

Baseline immunoglobulin G and immune function in non-Hodgkin lymphoma: a retrospective analysis

“…In Casulo 2013, 15% of patients had pre-rituximab hypogammaglobulinemia, of which 72% had further decreasing levels of immunoglobulins post treatment ( 17 ). The findings in the present study are consistent with existing literature which showed rituximab only increased risk of grade ≥3 infections in advanced-stage Hodgkin lymphoma ( 26 ). The authors hypothesize that although CD20 is expressed in increasing concentration during normal and malignant B-lymphocyte maturation, it is absent on pro-B cells and plasma cells explaining why rituximab does not directly impair immunoglobulin production ( 27 ).…”

Infections in children following chimeric antigen receptor T‐cell therapy for B‐cell acute lymphoblastic leukemia

“…Given its association with prolonged leukopenia, B-cell aplasia, and low immunoglobulin levels, understanding the infectious complications after CAR-T-cell infusion (CTI) is critical to informing appropriately targeted supportive care and prophylaxis strategies. 2 Patients receiving CAR-T-cell therapy, similar to those undergoing allogeneic hematopoietic stem cell transplant (HSCT), are considered to be at an increased risk of infection. 3 Data from the Summary Product Characteristics (SPC) reported a Grade 3 or more infection risk of between 19% to 35% in CAYA patients.…”

“…3 Data from the Summary Product Characteristics (SPC) reported a Grade 3 or more infection risk of between 19% to 35% in CAYA patients. 2 However, there are emerging data that suggest post-CTI infections may be more common. One CD19-CAR-T-cell study in CAYA patients (n = 39) reported up to 50% of patients experienced a total of 35 infections, with most occurring in the early post-infusion period between day 0 and day 28.…”

“…With the expanding commercial availability of CAR‐T‐cell products, such as Tisagenlecleucel (Kymriah), an increasing number of patients are expected to benefit from this novel immunotherapy. Given its association with prolonged leukopenia, B‐cell aplasia, and low immunoglobulin levels, understanding the infectious complications after CAR‐T‐cell infusion (CTI) is critical to informing appropriately targeted supportive care and prophylaxis strategies 2 …”

“…Patients receiving CAR‐T‐cell therapy, similar to those undergoing allogeneic hematopoietic stem cell transplant (HSCT), are considered to be at an increased risk of infection 3 . Data from the Summary Product Characteristics (SPC) reported a Grade 3 or more infection risk of between 19% to 35% in CAYA patients 2 . However, there are emerging data that suggest post‐CTI infections may be more common.…”