Treatment of infections in cancer patients: an update from the neutropenia, infection and myelosuppression study group of the Multinational Association for Supportive Care in Cancer (MASCC)

ABSTRACT

Introduction

Patients with hematological and advanced solid malignancies have acquired immune dysfunction, often exacerbated by treatment, posing a significant risk for the development of infections. This review evaluates the utility of current clinical and treatment guidelines, in the setting of management of infections in cancer patients.

Areas Covered

These include causes of infection in cancer patients, management of patients with high-risk and low-risk febrile neutropenia, management of low-risk patients in an outpatient setting, the role of granulocyte colony-stimulating factor (G-CSF) in the prevention and treatment of neutropenia-related infections, management of lung infections in various clinical settings, and emerging challenges surrounding the risk of infection in cancer patients treated with novel treatments. The literature search was performed by accessing PubMed and other databases, focusing on published clinical trials of relevant anti-cancer agents and diseases, primarily covering the recent past, but also including several key studies published during the last decade and, somewhat earlier in a few cases.

Expert Review

Notwithstanding the promise of gene therapy/gene editing in hematological malignancies and some types of solid cancers, innovations introduced in clinical practice include more discerning clinical management such as the generalized use of biosimilar formulations of G-CSF and the implementation of novel, innovative immunotherapies.

KEYWORDS:

• Antibiotic and host-directed therapies
• febrile neutropenia
• granulocyte colony-stimulating factor
• hematological malignancies
• opportunistic infections
• solid tumors

Article highlights

• Patients with cancer have a significant risk of infection resulting in considerable morbidity and mortality;

• Hematological malignancies are associated with immune dysfunction resulting in increased susceptibility to infection from an early stage;

• Patients with solid tumors have a predisposition for the development of infections later in the course of the disease and are associated with systemic inflammation and immunosuppression, immunosenescence, comorbidities, poor nutrition, smoking, and anatomical obstruction;

• Febrile neutropenia is considered a medical emergency and treated with empirical antibiotics to cover the most likely pathogens that will cause life-threatening infections in neutropenic patients;

• Low-risk febrile neutropenic patients with a MASCC risk index greater than 21 should be considered candidates for outpatient antibiotic therapy;

• Prophylactic use of G-CSF is a therapeutic strategy for maintaining the chemotherapy relative dose intensity during treatment, decreasing the incidence of severe neutropenia and FN, and improving treatment outcomes and quality of life;

• Amphotericin B formulations, newer triazoles (posaconazole, voriconazole, isavuconazole), and the echinocandins (caspofungin, micafungin, anidulafungin) are the preferred agents for the empiric treatment of neutropenic fever and patients with severe and invasive fungal infections;

• Immune checkpoint inhibitors do not appear to produce immunosuppression; however, high-dose corticosteroids used to treat immune-related adverse events increase the risks for opportunistic infections.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

B.L. Rapoport is supported by the Cancer Association of South Africa (CANSA) and the National Research Foundation (NRF) of South Africa.

Declaration of interest

B.L. Rapoport reports grants, personal fees and non-financial support from Sandoz, speaker engagements from Teva, speaker engagements from Amgen South Africa, speaker engagements from Mylan South Africa, during the conduct of the study. D.B. Johnson reports Ad board from Array Biopharma, grants and Ad board from BMS, Ad board from Catalyst Biopharma, Ad board from Jansen, Ad board from Iovance, Ad board from Merck, Ad board from Novartis, grants from Incyte, outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Author contributions

All of the authors contributed equally to the conceptualization of the manuscript; B.L. Rapoport, T. Cooksley, D.B. Johnson, V. Shannon and R. Anderson shared equally drafting of the manuscript, while T. Cooksley, B.L. Rapoport, D.B. Johnson and R. Anderson provided additional expert input and editorial oversight. All of the authors provided critical appraisal of the manuscript and approve of its submission.

Additional information

Funding

This paper was not funded.