Azole antifungals and new targeted therapies for hematological malignancy

Curr Opin Infect Dis. 2019 Dec;32(6):538-545. doi: 10.1097/QCO.0000000000000611.

Abstract

Purpose of review: With the introduction of new targeted therapies for hematological malignancies comes the challenges of both assessing the risk of developing an IFD while being treated with these agents, as well as managing the drug--drug interactions between azole antifungals and the agents.

Recent findings: New targeted therapies for hematological malignancy include chimeric antigen receptor T cells (CAR T cells), Bi-specific T-cell Engager (BiTE) blinatumomab, and the antibody-drug conjugate (ADC) of calicheamicin inotuzumab ozogamicin for acute lymphoblasic leukemia (ALL) and lymphoma; the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib and phosphatidylinositol 3-kinase (PI3Kδ) inhibitor idelalisib for lymphoma and graft-versus-host disease (GVHD); FMS-like tyrosine kinase 3 (FLT3) inhibitors, such as midostaurin, sorafenib and gilteritinib for acute myeloid leukemia (AML); and the BCL-2 inhibitor venetoclax for a range of hematological malignancies including lymphoma and leukemia. This review summarizes recommendations for IFD prophylaxis using these therapies and evidence for managing concomitant azole administration.

Summary: Whilst some evidence exists to guide IFD prophylaxis using new targeted therapies for hematological malignancies, there is an overall lack of descriptive, robust studies specifically describing IFD risk and management. With the emergence of novel agents, clinical judgment must be used to assess the risk of developing an IFD. Care must also be taken when administering azoles with drug--drug interactions, often requiring dose adjustment of the cancer therapies.

Publication types

  • Review

MeSH terms

  • Antifungal Agents / administration & dosage
  • Antifungal Agents / adverse effects
  • Antifungal Agents / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Azoles / administration & dosage
  • Azoles / adverse effects
  • Azoles / therapeutic use*
  • Chemoprevention
  • Clinical Decision-Making
  • Disease Management
  • Hematologic Neoplasms / complications*
  • Hematologic Neoplasms / epidemiology
  • Hematologic Neoplasms / therapy
  • Humans
  • Incidence
  • Invasive Fungal Infections / drug therapy*
  • Invasive Fungal Infections / epidemiology
  • Invasive Fungal Infections / etiology*
  • Molecular Targeted Therapy / adverse effects
  • Molecular Targeted Therapy / methods
  • Treatment Outcome

Substances

  • Antifungal Agents
  • Antineoplastic Agents
  • Azoles