Table 1.
Occurrence of Breakthrough Invasive Fungal Infections in 100 Patients With Leukemia Receiving Isavuconazole as a Single Agent
| Patient Age/Sex | Disease | Duration of Neutropenia, da | ISA Indication | ANC, Cells/μLb | Duration of ISA, d | b-IFI | Breakthrough Pathogen | ISA MIC, mcg/mLc | Outcomed |
|---|---|---|---|---|---|---|---|---|---|
| 45/F | R/R T-LGL | >14 | Secondary prophylaxis | <100 | 146 | Esophagitise | Candida albicans | ND | Alive |
| 71/M | R/R CLL | NA | Treatmentf | 500–1000 | 7 | Fungemiae | Candida parapsillosis | ND | Deceased |
| 52/M | R/R AML | 7–14 | Primary prophylaxis | <100 | 53 | Fungemiae | Trichosporon asahii | 0.5 | Deceased |
| 76/M | AMLg | >14 | Primary prophylaxis | 500–1000 | 14 | Disseminatede | Rhizopus spp. | 2 | Deceased |
| 61/F | R/R AML | NA | Primary prophylaxis | <100 | 34h | Pneumoniae | Mucorales spp. | ND | Alive |
| 30/M | R/R ALL | >14 | Secondary prophylaxis | <100 | 63 | Fungemiae | Candida guilliermondii | 1 | Deceased |
| 76/F | R/R AML | >14 | Treatmentf | 100–500 | 81 | Pneumoniae | Fusarium spp. | ND | Alive |
| 54/F | R/R AML | >14 | Treatmentf | <100 | 160 | Disseminatede | Candida krusei | 4 | Alive |
| 34/M | R/R AMLi | >14 | Primary prophylaxis | <10 | 24 | Fungemiae | Candida glabrata | 4 | Deceased |
| 51/F | R/R MDSi | 7–14 | Primary prophylaxis | >1000 | 41 | Fungemiae | Candida glabrata | 4 | Alive |
| 60/F | R/R ALL | NA | Treatmentf | 500–1000 | 157 | Pneumonia; fungemiae | Rhizopus spp.; C. glabrata | ND | Deceased |
| 61/M | R/R CLL | 7–14 | Treatmentf | 100–500 | 194 | Pneumoniaj | Rhizomucor spp. | ND | Deceased |
| 78/F | R/R AML | >14 | Treatmentf | <100 | 26 | Disseminatedj | Aspergillus spp. | ND | Alive |
Abbreviations: ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; ANC, absolute neutrophil count; b-IFI, breakthrough invasive fungal infection; CLL, chronic lymphocytic leukemia; ISA, isavuconazole; MDS, myelodysplastic syndrome; MIC, minimum inhibitory concentration; NA, nonapplicable; ND, not done; R/R, relapsed and/or refractory; T-LGL, T-cell large granular lymphocyte leukemia.
aAt the time of ISA initiation.
bAt the time of b-IFI diagnosis.
cMethod according to the National Committee for Clinical Laboratory Standards.
dOutcome 42 days after diagnosis of the b-IFI.
eProven b-IFI.
fMonotherapy for prior presumed (n = 4) or documented (n = 2) aspergillosis.
gNewly diagnosed.
hDiscontinued 3 days before b-IFI diagnosis.
iHistory of allogeneic stem cell transplantation.
jProbable b-IFI.