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Review
. 2021 Mar 5;7(3):186.
doi: 10.3390/jof7030186.

Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies

Ioannis Kyriakidis  1 , Eleni Vasileiou  1 , Claudia Rossig  2 , Emmanuel Roilides  3 , Andreas H Groll  4 , Athanasios Tragiannidis  1   4
Affiliations
Review

Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies

Ioannis Kyriakidis et al. J Fungi (Basel). .

Abstract

Since 1985 when the first agent targeting antigens on the surface of lymphocytes was approved (muromonab-CD3), a multitude of such therapies have been used in children with hematologic malignancies. A detailed literature review until January 2021 was conducted regarding pediatric patient populations treated with agents that target CD2 (alefacept), CD3 (bispecific T-cell engager [BiTE] blinatumomab), CD19 (denintuzumab mafodotin, B43, BiTEs blinatumomab and DT2219ARL, the immunotoxin combotox, and chimeric antigen receptor [CAR] T-cell therapies tisagenlecleucel and axicabtagene ciloleucel), CD20 (rituximab and biosimilars, 90Y-ibritumomab tiuxetan, ofatumumab, and obinutuzumab), CD22 (epratuzumab, inotuzumab ozogamicin, moxetumomab pasudotox, BiTE DT2219ARL, and the immunotoxin combotox), CD25 (basiliximab and inolimomab), CD30 (brentuximab vedotin and iratumumab), CD33 (gemtuzumab ozogamicin), CD38 (daratumumab and isatuximab), CD52 (alemtuzumab), CD66b (90Y-labelled BW 250/183), CD248 (ontuxizumab) and immune checkpoint inhibitors against CTLA-4 (CD152; abatacept, ipilimumab and tremelimumab) or with PD-1/PD-L1 blockade (CD279/CD274; atezolizumab, avelumab, camrelizumab, durvalumab, nivolumab and pembrolizumab). The aim of this narrative review is to describe treatment-related invasive fungal diseases (IFDs) of each category of agents. IFDs are very common in patients under blinatumomab, inotuzumab ozogamicin, basiliximab, gemtuzumab ozogamicin, alemtuzumab, and tisagenlecleucel and uncommon in patients treated with moxetumomab pasudotox, brentuximab vedotin, abatacept, ipilimumab, pembrolizumab and avelumab. Although this new era of precision medicine shows promising outcomes of targeted therapies in children with leukemia or lymphoma, the results of this review stress the necessity for ongoing surveillance and suggest the need for antifungal prophylaxis in cases where IFDs are very common complications.

Keywords: CAR T-cells; children; hematological malignancies; immune checkpoint inhibitors; invasive fungal diseases; leukemia; lymphoma; monoclonal antibodies.

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Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Schwartz R.S. Paul Ehrlich’s Magic Bullets. N. Engl. J. Med. 2004;350:1079–1080. doi: 10.1056/NEJMp048021. - DOI - PubMed
    1. Pui C.H., Yang J.J., Hunger S.P., Pieters R., Schrappe M., Biondi A., Vora A., Baruchel A., Silverman L.B., Schmiegelow K., et al. Childhood acute lymphoblastic leukemia: Progress through collaboration. J. Clin. Oncol. 2015;33:2938–2948. doi: 10.1200/JCO.2014.59.1636. - DOI - PMC - PubMed
    1. Fernández-Ruiz M., Meije Y., Manuel O., Akan H., Carratalà J., Aguado J.M., Delaloye J. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: An infectious diseases perspective (Introduction) Clin. Microbiol. Infect. 2018;24:S2–S9. doi: 10.1016/j.cmi.2018.01.029. - DOI - PubMed
    1. Kyriakidis I., Tragiannidis A., Zündorf I., Groll A.H. Invasive fungal infections in paediatric patients treated with macromolecular immunomodulators other than tumour necrosis alpha inhibitors. Mycoses. 2017;60:493–507. doi: 10.1111/myc.12621. - DOI - PubMed
    1. Brown A.J.P., Gow N.A.R., Warris A., Brown G.D. Memory in Fungal Pathogens Promotes Immune Evasion, Colonisation, and Infection. Trends Microbiol. 2019;27:219–230. doi: 10.1016/j.tim.2018.11.001. - DOI - PubMed