A review of prophylactic regimens to prevent invasive fungal infections in hematology patients undergoing chemotherapy or stem cell transplantation

ABSTRACT

Introduction

The recent introduction of targeted therapies, including monoclonal antibodies, tyrosine-kinase inhibitors, and immunotherapies has improved the cure rate of hematologic patients. The implication of personalized treatment on primary antifungal prophylaxis will be discussed.

Areas covered

We reviewed the literature for clinical trials reporting the rate of invasive fungal infections during targeted and cellular therapies and stem cell transplant, and the most recent international guidelines for primary antifungal prophylaxis.

Expert opinion

As the use of personalized therapies is growing, the risk of invasive fungal infection has emerged in various clinical settings. Therefore, it is possible that the use of mold-active antifungal prophylaxis would spread in the next years and the risk of breakthrough infections would increase. The introduction of new antifungal agents in the clinical armamentarium is expected to reduce clinical unmet needs concerning the management of primary antifungal prophylaxis and improve outcome of patients.

KEYWORDS:

• Antifungal prophylaxis
• allogeneic transplant
• acute leukemia
• lymphoproliferative disease
• cellular therapy

Article highlights

• Indication to PAP with mold-active azoles during the first induction therapy for patients with AML is confirmed in all international guidelines.

• The need for PAP in patients with AML treated with demethylating agents and venetoclax has been balanced with the risk of severe side effects due to DDIs.

• The introduction of conjugated and bispecific antibodies in the treatment of patients with ALL has not increased the risk of IFI.

• The introduction of BTK, PI3K-δ, and BCL-2 inhibitors and new generation MoAbs has markedly increased the risk of IFI in patients with CLL.

• Systematic studies and consensus guidelines regarding PAP in CAR-T setting are lacking physicians should consider the administration of PAP on a case-by-case basis.

• Deteriorating patients’ conditions should prompt clinical judgment over possible breakthrough IFI.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.