Table 3.

Summary of CNS aspergillosis cases in patients treated with ibrutinib.

Study	Patient	Prior Oncologic Treatment	Aspergillus Species	Time from Ibrutinib Initiation to Diagnosis of CNS Aspergillosis (months)	Antifungal Treatment	Patient Outcome at Time of Publication
Gaye et al. [17]	Patient 1: CLL	Obinituzumab, chlorambucil, rituximab, bendamustine	A. fumigatus	<1	Voriconazole; ibrutinib discontinued	Alive
	Patient 2: CLL	Corticosteroids	A. fumigatus	2	Voriconazole and amphotericin B; ibrutinib continued	Alive
Ruchlemer et al. [18]	Patient 1: CLL	Corticosteroids	NR	1	NR	Dead
	Patient 2: CLL	Corticosteroids	NR	2	LAMB and voriconazole; ibrutinib discontinued	Alive
	Patient 3: CLL	Corticosteroids	NR	2	NR	Alive
Jain et al. [19]	CLL	Rituximab	NR	2	NR	Deceased
Baron et al. [3]	CLL	Fludarabine, CP, rituximab	A. nidulans	<1	Voriconazole; ibrutinib discontinued	Alive
Beresford et al. [20]	CLL	Fludarabine, CP, bendamustine, rituximab	A. fumigatus	12	Voriconazole subsequently switched to posaconazole; ibrutinib discontinued	Alive
Ghez et al. [13]	11 patients	Median number of prior therapies: 2	NR	Median 3 monthsb	NR	NR: Total mortality 52% for all patients with IFI
Ruchlemer et al. [6]	9 patients; CLLa or NHL	Median number of prior therapies: 3 (no patients were treatment-naïve prior to starting ibrutinib)	NR	Median 1.5 monthsb	NR	NR: Total mortality 69% for all patients with IFI (including those with non-CNS disease)
Lionakis et al. [14]	Patient 1: PCNSL	Corticosteroids	A. fumigatus	<1	NR	Deceased
	Patient 2: PCNSL	4 prior therapies, Corticosteroids, on TEDDi-R	A. fumigatus	<1		Deceased
	Patient 3: PCNSL	4 cycles TEDDi-R	A. fumigatus	3		Deceased
	Patient 4: PCNSL	Corticosteroids; 1 cycle TEDDi-R	A. fumigatus	<1		Alive
Present Case	62yo M CLL	None	A. fumigatus	<1	Voriconazole, ibrutinib discontinued	Alive

CLL chronic lymphocytic leukemia; NR not reported; LAMB liposomal amphotericin B; NHL Non-Hodgkin Lymphoma; PCNSL Primary CNS Lymphoma; CP cyclophosphamide, TEDDi-R Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib, and Rituximab.

^a2 of the patients included in this study were also included in reference [21].

^bAnalysis included all patients with IFI on ibrutinib regardless of site of infection.