Table 2.

Breakthrough Invasive Fungal Infections During Isavuconazole Prophylaxis

Patient	Date of Onset	Age/Sex	Underlying Malignancy	HCT	Prophylaxis Indication	Chemotherapy	Pathogen	Mycological Diagnosis	EORTC/MSG Classification	Duration of Neutropenia, da	Duration Prophylaxis, da	Trough Level, μg/mLb	ISA MIC, μg/mL	Therapy	Outcomec
1	30 Oct 2016	74/F	AML	N	Induction	FLAG-IDA	Aspergillus spp	Serum GM	Probable	26	10	6.3	ND	ISA	Death (34)
2	30 Nov 2016	71/M	AML	N	Induction	Study	Aspergillus spp	Serum GM	Probable	18	15	ND	ND	ISA	Alive
3	27 Mar 2017	30/M	R/R AML	N	Reinduction	Decitabine	Aspergillus fumigatus	BALF GM, BALF PCR	Probable	180	125	3.3	NDd	Amb	Alive
4	5 Apr 2017	57/M	R/R AML	N	Reinduction	FLAG-IDA	Fusarium dimerum	BALF culture	Probable	25	8	ND	NDe	ISA	Death (8)
5	29 Apr 2017	45/F	R/R AML	Y	Reinduction	FLAG-IDA	Fusarium spp	Blood culture	Proven	9	9	ND	NDf	Amb	Alive
6	5 May 2017	64/F	R/R AML	N	Reinduction	7 + 3	A. fumigatus	BALF GM, BALF PCR	Probable	38	13	3.7	NDd	VOR	Alive
7	28 May 2017	65/M	R/R AML	N	Reinduction	FLAG-IDA	A. fumigatus	BALF GM, BALF PCR	Probable	38	40	4.3	NDd	VOR	Death (19)
8	5 Jul 2017	60/M	R/R AML	N	Reinduction	MEC	Rhizopus microsporus or azygosporus	Histopathology, Lung tissue PCR	Proven	11	14	ND	ND	Amb, POS	Alive
9	13 Aug 2017	64/F	MF	Y	Pre-HCT neutropenia	NA	A. fumigatus	Sputum culture	Probable	16	12	ND	0.5	Mica	Death (12)
10	3 Sept 2017	67/M	R/R ALL	Y	Reinduction	FLAG-IDA	Syncephalastrum monosporum or racemosum	BALF culture, BALF PCR	Probable	27	22	ND	2	POS	Death (14)
11	8 Sept 2017	53/F	AML	N	Induction	7 + 3	A. fumigatus	BALF PCR	Possible w/PCR+	21	20	3.4	ND	Mica	Death (27)
12	30 Jul 2018	25/M	R/R ALL	N	Targeted therapy	CAR-T	Candida glabrata	Blood culture	Proven	82	14	ND	NDg	Mica	Death (7)

Abbreviations: 7 + 3, cytarabine, anthracycline; ALL, acute lymphocytic leukemia; Amb, AmBisome; AML, acute myeloid leukemia; BALF, bronchoalveolar lavage fluid; CAR-T, chimeric antigen receptor T-cell therapy; EORTC/MSG, European Organization for Research and Treatment of Cancer/Invasive Fungal Infection Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group; F, female; FLAG-IDA, fludarabine, cytarabine, idarubicin; GM, galactomannan; HCT, hematopoietic cell transplant; ISA, isavuconazole; M, male; MEC, mitoxantrone, etoposide, cytarabine; MF, myelofibrosis; MIC, minimum inhibitory concentration; Mica, micafungin; N, no; NA, not applicable; ND, not determined; PCR, polymerase chain reaction; POS, posaconazole; R/R, relapsed/refractory; VOR, voriconazole; Y, yes.

^aPrior to breakthrough invasive fungal infection (bIFI).

^bPerformed within 72 hours of bIFI.

^cDefined as occurring within 42 days of date of onset of bIFI, with interval (days) from date of onset to date of death provided when applicable.

^d CYP51A gene sequencing performed (refer to text and Supplementary Table 1).

^eMICs: itraconazole (ITRA) ≥16, POS ≥16, VOR = 8.

^fMIC ≥16 for ITRA, POS, and VOR.

^gMICs: fluconazole = 16, POS = 2, ITRA = 1.