Table 1.

Reported Cases of IFI During Ibrutinib Therapy (n = 41)^a

Pathogen or Type of IFI	Time After Treatment	Site of infection	Type and Status of Underlying Cancer	Age, y/Sex	Concomitant Use of Corticosteroids/ Prior Treatment	Outcome	Reference
Cryptococcosis	NA	NA	MCL/PD	NA	NA/NA	NA	Wang et al [7]
Cryptococcus neoformans	1 mo	Lungs, blood	CLL/PR	68/M	No/chlorambucil and prednisone	Alive	Okamoto et al [22]
C. neoformans	1 mo	CNS, lungs	Lymphoplasmacytic lymphoma/PD	88/M	No/rituximab, benadmustine	Alive	Messina et al [19]
C. neoformans	3 wk	CNS, lungs, blood	CLL/PD	54/M	No/fludarabine, ritiximab, cyclophosphamide	Dead	Messina et al [19]
C. neoformans	2 mo	CNS, skin	WM/PD	74/F	No/fludarabine, ritiximab, cyclophosphamide, dexamethasone, and idelasilib	Dead	Baron et al [18]
PJP	NA	NA	MCL/PD	NA	NA/yes (NA)	NA	Wang et al [7]
PJP	1.9 mo	Lungs	CLL/SD	69/M	No/no (frontline)	Alive	Ahn et al [15]
PJP	23.6 mo	Lungs	CLL/SD	68/M	Yesb/no (frontline)	Alive	Ahn et al [15]
PJP	1.9 mo	Lungs	CLL/SD	72/M	No/no (frontline)	Alive	Ahn et al [15]
PJP	6 mo	Lungs	CLL/PD	78/M	No/yes (NA)	Alive	Ahn et al [15]
PJPb	11.6 mo	Lungs	CLL/SD	70/M	No/no (frontline)	Alive	Ahn et al [15]
Histoplasmosis	NA	NA	MCL/PD	NA	NA/NA	NA	Wang et al [7]
IAc	1 month	CNS	CLL/PD	NA	Yes/NA	Dead	Ruchlemer et al [13]
IA	2 mo	CNS	CLL/PD	NA	Yes/NA	Alive	Ruchlemer et al [13]
IA	2 mo	CNS	CLL/PD	NA	Yes/NA	Alive	Ruchlemer et al [13]
IA	6 wk	Lungs	CLL/PD	62/M	No/fludarabine and rituximab	Alive	Arthus et al [14]
IA	2 wk	CNS, lungs	PCNSL	76/F	Yes/no (frontline)	Dead	Lionakis et al [12]
IA	2 wk	CNS, lungs	PCNSL	65/M	Yes/no (frontline)	Dead	Lionakis et al [12]
IA	3 mo	CNS, lungs	PCNSL	87/F	No/no (frontline)	Dead	Lionakis et al [12]
IAd	4 mo	Lungs	PCNSL	60/M	Yes/no (frontline)	Alive	Lionakis et al [12]
IAd	2 mo	Lungs	PCNSL	53/M	No/no (frontline)	Alive	Lionakis et al [12]
IAd	[1 mo	Lungs	PCNSL	64/M	Yes/no (frontline)	Alive	Lionakis et al [12]
IA	2 wk	CNS, lungs	PCNSL	49/M	Yes/no (frontline)	Alive	Lionakis et al [12]
Aspergillus nidulans	3 wk	Sinusitis, CNS	CLL/PD	75/F	No/fludarabine, ritiximab, cyclophosphamide	Alive	Baron et al [18]
Extensive aspergillosis	2.1 mo	Lungs, brain	CLL/PD	76/NA	No/rituximab	Dead	Jain et al [6]
Mucormycosis, aspergillosis	7 mo	Lungs	CLL/PD	67/M	No/rituximab, fludarabine	Dead	Kreiniz et al [23]
Mucormycosis	NA	Skin	CLL/NA	NA	NA/no	Dead c	Figuera Castro et al [17]
Fusarium solani	1.5 mo	Disseminated	CLL/PD	46/M	No/anti-CD20 mAb and bendamustin	Alive	Chan et al [20]

Abbreviations: CLL, chronic lymphocytic leukemia; CNS, central nervous system; F, female; IA, invasive aspergillosis; IFI, invasive fungal infection; M, male; mAb, monoclonal antibody; MCL, mantle cell lymphoma; NA, not available; PCNSL, primary central nervous system lymphoma; PD, progressive disease; PJP, Pneumocystis jirovecii pneumonia; PR, partial response; SD, stable disease; WM, Waldenström macroglobulinemia.

^aFive additional cases of IFIs in patients with LLC and MCL were reported at a single university cancer center during a 1-year study period, including 2 cases of IA and 1 case each of mucormycosis, PJP, and cryptococcosis, all occurring within 3 months of ibrutinib therapy (Protin et al [16]). Dimopoulos et al [9] reported 1 case of IA in a patient with WM; Byrd et al [10], 2 cases of pulmonary IA; Byrd et al [11], 1 case of cryptococcal infection in a patient with CLL; O’Brien et al [21], 1 case of PJP in a patient with CLL; Choquet et al [24], 2 cases of pulmonary IA in patients with PCNSL; and Grommes et al [25], 1 case of CNS IA in a patient with PCNSL. Information on infectious disease outcome and patient clinical characteristics was not available for these cases.

^bThe patient received an intermittent course of low-dose oral corticosteroids.

^cDeath due to unrelated causes.

^dPossible IA.