Invasive aspergillosis with pulmonary and central nervous system involvement during ibrutinib therapy for relapsed chronic lymphocytic leukaemia: case report

Peri, Anna Maria; Bisi, Luca; Cappelletti, Anna; Colella, Elisa; Verga, Luisa; Borella, Chiara; Foresti, Sergio; Migliorino, Guglielmo Marco; Gori, Andrea; Bandera, Alessandra

doi:10.1016/j.cmi.2018.01.028

Cited by 13 publications

(9 citation statements)

References 5 publications

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“…Another retrospective study has shown 37.2% of patients receiving ibrutinib for lymphoid cancer developed invasive fungal infection 9. Multiple case reports also support an association of invasive aspergillosis with ibrutinib therapy,10–14 with several case reports suggesting an association with cryptococcal infection 14–20. Mucormycosis and Pneumocystis jirovecii with ibrutinib therapy have also been described 21–23…”

Section: Discussionmentioning

confidence: 98%

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Invasive aspergillosis complicating treatment with tyrosine kinase inhibitors

et al. 2019

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We describe three cases of pulmonary aspergillosis (PA) in three patients without traditional risk factors for invasive aspergillosis infection, such as prolonged neutropenia or high dose systemic corticosteroid therapy. All three patients developed PA while taking tyrosine kinase inhibitors (TKI) and sustained greater clinical improvement once TKI were withdrawn. Our case series supports the theory TKI treatment can increase susceptibility to PA without causing neutropenia. Recognition that TKI treatment may predispose to invasive aspergillosis will allow for rapid recognition of affected patients and more effective management of future cases.

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Section: Discussionmentioning

confidence: 98%

“…More indolent forms of PA are associated with chronic lung disease and milder immunodeficiencies. Here we describe three cases of PA developing in patients receiving TKI treatment, an association that has only recently been reported with ibrutinib 8–14…”

Section: Introductionmentioning

confidence: 86%

Invasive aspergillosis complicating treatment with tyrosine kinase inhibitors

et al. 2019

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“…Thereafter, an increasing number of reports of IFD and other opportunistic infections during ibrutinib treatment have been published, with Aspergillus species, being the most frequent pathogens . Epidemiological data concerning fungal infections in patients with lymphoproliferative disorders are scarce and are mainly based on the Italian SEIFEM‐2004 study which reported an annual incidence of invasive moulds and yeast infections of 0.4% and 0.1%, respectively, for CLL and 0.9% and 0.7%, respectively, for NHL…”

Section: Introductionmentioning

confidence: 99%

“…7 Thereafter, an increasing number of reports of IFD and other opportunistic infections during ibrutinib treatment have been published, with Aspergillus species, being the most frequent pathogens. 6,[8][9][10][11][12][13][14][15][16][17][18][19][20] Epidemiological data concerning fungal infections in patients with lymphoproliferative disorders are scarce and are mainly based on the Italian SEIFEM-2004 study which reported an annual incidence of invasive moulds and yeast infections of 0.4% and 0.1%, respectively, for CLL and 0.9% and 0.7%, respectively, for NHL. 21 This retrospective, multi-national survey was undertaken to add a systematic collection of data to the accumulating reports of ibrutinib-associated IFD in CLL and NHL patients and to determine the prevalence and clinical features of IFD in this setting.…”

Section: Introductionmentioning

confidence: 99%

Ibrutinib‐associated invasive fungal diseases in patients with chronic lymphocytic leukaemia and non‐Hodgkin lymphoma: An observational study

Ruchlemer

Ben‐Ami

Bar-Meir

et al. 2019

Mycoses

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Summary Background Invasive fungal diseases (IFD) are life‐threatening infections most commonly diagnosed in acute leukaemia patients with prolonged neutropenia and are uncommonly diagnosed in patients with lymphoproliferative diseases. Objectives Following the initial report of aspergillosis diagnosed shortly after beginning ibrutinib for chronic lymphocytic leukaemia, a survey was developed to seek additional cases of IFD during ibrutinib treatment. Methods Local and international physicians and groups were approached for relevant cases. Patients were included if they met the following criteria: diagnosis of chronic lymphocytic leukaemia/non‐Hodgkin lymphoma; proven or probable IFD; and ibrutinib treatment on the date IFD were diagnosed. Clinical and laboratory data were captured using REDCap software. Result Thirty‐five patients with IFD were reported from 22 centres in eight countries: 26 (74%) had chronic lymphocytic leukaemia. The median duration of ibrutinib treatment before the onset of IFD was 45 days (range 1‐540). Aspergillus species were identified in 22 (63%) of the patients and Cryptococcus species in 9 (26%). Pulmonary involvement occurred in 69% of patients, cranial in 60% and disseminated disease in 60%. A definite diagnosis was made in 21 patients (69%), and the mortality rate was 69%. Data from Israel regarding ibrutinib treated patients were used to evaluate a prevalence of 2.4% IFD. Conclusions The prevalence of IFD among chronic lymphocytic leukaemia/non‐Hodgkin lymphoma patients treated with ibrutinib appears to be higher than expected. These patients often present with unusual clinical features. Mortality from IFD in this study was high, indicating that additional studies are urgently needed to identify patients at risk for ibrutinib‐associated IFD.

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“…Prolongation of survival with these agents comes with the cost of increased risk of bacterial and fungal infections. Among the TKIs, ibrutinib, tofacitinib, and dasatinib carry a black box warning for opportunistic infections including pneumocystis, aspergillosis, and reactivation of tuberculosis, varicella-zoster and cytomegalovirus infections [7][8][9][10][11][12][13][14][15][16]. Sunitinib specifically targets members of the split-kinase domain family of receptor tyrosine kinases (RTKs) including the vascular endothelial growth factor receptors type1 and 2 (VEGFR 1,2), platelet-derived growth factor receptors (PDGFR α,β), fibroblast growth factor receptor (FGFR1), FMS-related tyrosine kinase (FLT3), stem cell factor receptor (c-KIT), rearranged during transfection (RET) kinase and colony-stimulating factor 1 receptor, resulting in direct and indirect B and T cell dysfunction at various levels [1,2].…”

Section: Discussionmentioning

confidence: 99%

Sunitinib Use for Metastatic Renal Cell Carcinoma Associated with Necrotizing Cavitary Pulmonary Aspergillosis with Aspergillus flavus: Case Report and Review of Literature

Natesan

2019

IJMPCR

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Sunitinib associated chronic necrotizing cavitary pulmonary aspergillosis has rarely been reported in literature. This article describes a patient with biopsy proven papillary renal cell carcinoma initially treated by radical nephrectomy. He presented about 8 months later with progressively worsening abdominal pain, headache, weight loss of 40 pounds and investigation revealed extensive retroperitoneal and mediastinal lymphadenopathy with brain metastasis. He was evaluated by oncology and started on cycles of sunitinib with dexamethasone, which he took for about 6+ months. He presented to the hospital in respiratory distress requiring intubation and ICU admission and CT scan of thorax revealed a new large consolidation with necrosis and a cavity. Given suspicion of opportunistic fungal infection with sunitinib, he was started on empiric Vancomycin, Zosyn and Voriconazole. He underwent bronchoscopy, bronchoalveolar lavage and cultures revealed Aspergillus flavus. Subsequently serum and BAL (Bronchoalveolar Lavage) galactomannan were reported positive as well. Given poor prognosis, patient’s family elected for comfort measures.

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Invasive aspergillosis with pulmonary and central nervous system involvement during ibrutinib therapy for relapsed chronic lymphocytic leukaemia: case report

Cited by 13 publications

References 5 publications

Invasive aspergillosis complicating treatment with tyrosine kinase inhibitors

Invasive aspergillosis complicating treatment with tyrosine kinase inhibitors

Ibrutinib‐associated invasive fungal diseases in patients with chronic lymphocytic leukaemia and non‐Hodgkin lymphoma: An observational study

Sunitinib Use for Metastatic Renal Cell Carcinoma Associated with Necrotizing Cavitary Pulmonary Aspergillosis with Aspergillus flavus: Case Report and Review of Literature

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