Table 2.
Opportunistic infections in patients receiving ibrutinib
| Pathogen | Site | Age/sex | Cancer | Time since commencing ibrutinib (months) | Concurrent treatment/previous treatments | Hypogammaglobulinaemia/ lymphopenia/neutropenia |
Treatment | Outcome | Reference |
| Aspergillus fumigatus | Lung | 62/M | CLL | 1.5 | None/fludarabine+ rituximab (timing NR) |
NR/absent (CD4 T-cell count: NR)/absent | Voriconazole (duration NR) | Died (5 months later due to CLL) | 38 |
| Aspergillus nidulans | Cavernous sinus Orbit Sphenoid bone Sphenoid sinus |
75/F | CLL | 0.82 | Rituximab/R FC × 6 cycles (December 2012–May 2013) | Absent/absent (CD4 T-cell count: NR)/absent | Voriconazole (duration NR) | Survived | 39 |
| Aspergillus spp | CNS Lung |
76/NR | CLL | 2.1 | Rituximab/2 other therapies not specified | NR | NR | Died | 40 |
| Aspergillus spp | Lung | NR | CLL | NR | NR | NR | NR | NR | 41 |
| Aspergillus spp | Lung | 65/F | CLL+DLBCL (EBV+) | 1 | None/R ESHAP then R-EPOCH (September 2013–March 2014) | NR/NR/absent | Voriconazole (duration NR) | Survived | 42 |
| Aspergillus spp | CNS (brain abscess) | NR | CLL | 1 | Glucocorticoids/NR | NR | NR | Died | 43 |
| Aspergillus spp | CNS (brain abscess) | NR | CLL | 2 | Glucocorticoids/NR | NR | LAMB (duration NR) then voriconazole for 12 months | Survived | 43 |
| Aspergillus spp | CNS (brain abscess) | NR | CLL | 2 | Glucocorticoids/NR | NR | LAMB (duration NR) | Survived | 43 |
| Aspergillus spp | CNS Lung |
76/F | PCNSL | 0.5 | Glucocorticoids/none | NR | NR | Died | 5 |
| Aspergillus spp | CNS Lung |
65/M | PCNSL | 0.5 | Glucocorticoids/none | NR | NR | Died | 5 |
| Aspergillus spp | CNS Lung |
87/F | PCNSL | 3 | None/none | NR | NR | Died (due to PCNSL) | 5 |
| Aspergillus spp | CNS Lung |
49/M | PCNSL | 0.5 | Glucocorticoids/none | NR | NR | Survived | 5 |
| Aspergillus spp | Lung | 60/M | PCNSL | 4 | Glucocorticoids/none | NR | NR | Survived | 5 |
| Aspergillus spp | Lung | 53/M | PCNSL | 2 | None/none | NR | NR | Survived | 5 |
| Aspergillus spp | Lung | 64/M | PCNSL | 1 | Glucocorticoids/none | NR | NR | Survived | 5 |
| Aspergillus spp | NR | NR | WM | NR | None/rituximab, other therapies not specified | NR | NR | NR | 44 |
| Aspergillus spp | Lung | NR | PCNSL | NR | NR/other therapies not specified | NR | NR | Survived | 45 |
| Aspergillus spp | CNS | NR | PCNSL | NR | NR/other therapies not specified | NR | NR | NR | 46 |
|
Aspergillus spp Mucormycosis |
Lung | 67/M | CLL | 7 | None/R-F (2011) | Present/absent (CD4 T-cell count: NR)/present | Voriconazole (duration NR) | Died | 47 |
| Cryptococcus neoformans | Blood Lung |
68/F | CLL | 1 | None/chlorambucil+prednisolone×6 cycles (2012–2014) | Present/absent (CD4 T-cell count: NR)/absent | LAMB+flucytosine (2 weeks) then fluconazole (duration NR) | Survived | 48 |
| Cryptococcus spp | Blood Skin (diffuse purpuric rash) |
71/M | MCL | 4 | Bortezomib (1 month previously)/R bendamustine×3 cycles (5–7 months previously), ibrutinib (1–5 months previously) | NR/NR/NR | Fluconazole then LAMB+flucytosine (duration NR) | Died | 49 |
| Cryptococcus neoformans | CNS (meningo-encephalitis) Skin (leg abscess) |
74/F | WM | 2 | None/bortezomib+R-CHOP, R-FC, R-CD (2005–August 2014) then idelalisib (September 2014–March 2015) | Present/NR/absent | LAMB (duration NR) | Died | 39 |
| Cryptococcus neoformans | Blood CNS (meningitis) Lung |
54/M | CLL | 1 | None/R FC (2014–2015) | NR/absent (CD4 T-cell count: NR)/absent | LAMB+flucytosine for 2 weeks then LAMB+fluconazole for 2 weeks | Died | 50 |
| Cryptococcus neoformans | CNS (meningitis) Lung |
88/M | WM | 0.75 | None/rituximab (2008), R-bendamustine (2012) | NR/present/absent | LAMB+flucytosine for 2 weeks then fluconazole lifelong | Survived | 50 |
| Cryptococcus spp | NR | NR | MCL | NR | NR | NR | NR | NR | 51 |
| Cryptococcus spp | Lung | NR | CLL | NR | NR | NR | NR | NR | 52 |
| Fusarium solani | Disseminated (skin lesions) | 56/M | CLL | 1.5 | None/FMD×6 cycles (2007), R-CHOP×6 cycles then ibritumomab tiuxetan (2010), obinutuzumab+bendamustine×6 cycles (2014) | Present/absent (CD4 T-cell count: NR)/present | Voriconazole for 6 weeks then prophylaxis | Survived | 53 |
| Histoplasma capsulatum | NR | NR | MCL | NR | NR | NR | NR | NR | 51 |
| JC virus | CNS (progressive multifocal leukoencephalopathy) | 65/M | CLL | 1.75 (ibrutinib ceased 1 month prior due to pneumonia) | None/FC×5 cycles (2008), R-bendamustine×2 cycles (2012), cyclophosphamide+epirubicin+prednisolone×6 cycles (2013) | Present/NR/NR | Mefloquine+mirtazapine for 7 weeks | Died (7 weeks later from presumed aspiration pneumonia) | 54 |
| Mycobacterium tuberculosis | CNS (brain abscesses) Lung (miliary) Spine |
64/M | CLL | 1 | None/7 other therapies including allogeneic haematopoietic stem cell transplantation | NR/absent (CD4 T-cell count: normal)/absent | Rifampicin, isoniazid, ethambutol and pyrazinamide (duration NR) | Survived | 55 |
| Pneumocystis jirovecii | NR | NR | MCL | NR | NR | NR | NR | NR | 51 |
| Pneumocystis jirovecii | Lung | 69/M | CLL | 1.9 | None/none | NR/absent (CD4 T-cell count: NR)/absent | Trimethoprim+sulfamethoxazole for 21 days then prophylaxis | Survived | 56 |
| Pneumocystis jirovecii | Lung | 68/M | CLL | 23.6 | Glucocorticoids/none | Absent (IVIg replacement)/absent (CD4 T-cell count: 551/µL)/absent | Trimethoprim+sulfamethoxazole then atovaquone for 21 days then no prophylaxis | Survived | 56 |
| Pneumocystis jirovecii | Lung | 72/M | CLL | 1.9 | None/none | NR/absent (CD4 T-cell count: NR)/absent | Trimethoprim+sulfamethoxazole for 21 days then no prophylaxis | Survived | 56 |
| Pneumocystis jirovecii | Lung | 78/M | CLL | 6 | None/other therapies not specified | Absent/absent (CD4 T-cell count: 966/µL)/absent | Trimethoprim+sulfamethoxazole for 14 days then no prophylaxis | Survived | 56 |
| Pneumocystis jirovecii | Lung | 70/M | CLL | 11.6 | None/none | Absent/absent (CD4 T-cell count: 734/µL)/absent | Trimethoprim+sulfamethoxazole for 21 days then no prophylaxis (then prophylaxis 12 months later) | Survived | 56 |
| Pneumocystis jirovecii | Lung | NR | CLL | NR | None/other therapies not specified | NR | NR | NR | 57 |
| ‘Recurrent fungal pneumonia’ | Lung | 64/NR | CLL | 20 | None/3 other therapies not specified | NR | NR | Died | 40 |
| Mucor spp | Sinus | 79/M | CLL | 20 | None/NR | Present (IgG level: 2.07 g/L)/present (total lymphocyte count: 320 cells/µL)/present (neutrophil count: 520 cells/µL) | Isavuconazole+LAMB for 7 days then isavuconazole (duration NR) | Survived | 58 |
| Zygomycete | Skin | NR | CLL | NR | None/NR | NR | LAMB (duration NR) then posaconazole (duration NR) | Died (due to CLL) | 59 |
CLL, chronic lymphocytic leukaemia; CNS, central nervous system; DLBCL, diffuse large B-cell lymphoma; EBV, Epstein-Barr virus; FMD, fludarabine+mitoxantrone+dexamethasone; JC virus, John Cunningham virus; LAMB, liposomal amphotericin B; MCL, mantle cell lymphoma; NR, not reported; PCNSL, primary central nervous system lymphoma; R-bendamustine, rituximab+bendamustine; R-CHOP, rituximab+cyclophosphamide+hydroxydaunorubicin+vincristine+prednisolone; R-EPOCH, rituximab+etoposide+prednisolone+vincristine+cyclophosphamide+hydroxydaunorubicin; R-ESHAP, rituximab+etoposide+methylprednisolone+cytarabine+cisplatin; R-F, rituximab+fludarabine; R-FC, rituximab+fludarabine+cyclophosphamide; WM, Waldenstrӧm macroglobulinaemia.