Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib

Ahn, Inhye E.; Jerussi, Theresa; Farooqui, Mohammed; Tian, Xin; Wiestner, Adrian; Gea-Banacloche, Juan

doi:10.1182/blood-2016-06-722991

Cited by 152 publications

(103 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Once ibrutinib therapy has been initiated, patients should be monitored for fever, neutropenia and infections as part of their routine check at every clinic visit and all treatment‐emergent infections should be carefully assessed for aetiology, treated vigorously and the use of growth factors should be considered. Based on recent reports describing a small number of cases, physicians should be also be vigilant to exclude the possibility of opportunistic infections, such as Pneumocystis (jirovecii) pneumonia (PJP) (Ahn et al , ; Arthurs et al , ); however, prophylaxis for all patients is not recommended. For low‐grade infections, the authors recommend continuation of ibrutinib therapy and dose adjustments need only be considered for the duration of anti‐infective treatment if there is the potential for DDI with antimicrobial agents that are moderate/strong CYP3A4 inhibitors (e.g.…”

Section: Resultsmentioning

confidence: 99%

Optimising outcomes for patients with chronic lymphocytic leukaemia on ibrutinib therapy: European recommendations for clinical practice

et al. 2018

View full text Add to dashboard Cite

Ibrutinib is indicated in Europe for the treatment of several B-cell malignancies, including chronic lymphocytic leukaemia (CLL). However, despite the high efficacy and favourable toxicity profile of ibrutinib, recent data suggest that it is not always administered optimally in clinical practice, with an increased tendency for dose reduction and a higher frequency of discontinuation. An expert panel of European haematologists was convened to identify practical issues pertinent to physicians involved in the therapeutic management of ibrutinib-treated CLL patients and here we outline the findings. Practical management recommendations are given for treating patients with ibrutinib and clinical considerations for the management of adverse events (AEs) that can be associated with ibrutinib treatment are addressed. This article highlights that patients should be monitored for treatment emergent adverse events, most of which are mild, transient and generally occur early in therapy and that, even with more challenging AEs, patients can often be maintained on therapy with minimal disruption through careful management. The necessity to use the correct ibrutinib dose, along with increased awareness, vigilance, mitigation and management of AEs, are all recommended to maximise outcomes for CLL patients treated with ibrutinib.

show abstract

Section: Resultsmentioning

confidence: 99%

Optimising outcomes for patients with chronic lymphocytic leukaemia on ibrutinib therapy: European recommendations for clinical practice

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Although we did not specifically test cellular immune cell functions, all four patients with infection demonstrated significantly depressed CD4 counts and low NK cell counts. Interestingly, Ahn et al recently reported an increased rate of Pneumocystis jirovecii pneumonia in previously untreated CLL patients on single-agent ibrutinib [23]. Infections occurred at a median of 6 months on ibrutinib, and were not associated with decreased IgG or CD4 T cell levels.…”

Section: Discussionmentioning

confidence: 99%

Atypical Infections in Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma Patients Treated with Ibrutinib

Rimon¹,

Wienberger²,

Herzog-Tzarfati³

et al. 2017

J Blood Lymph

View full text Add to dashboard Cite

Ibrutinib is an oral Bruton's tyrosine kinase inhibitor with clinical efficacy in several B cell malignancies. In a pooled analysis of clinical trials evaluating ibrutinib, grade 3-4 infections were reported in 14% of patients. We screened consecutive patients on ibrutinib therapy for chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) for infectious complications. Patients were hospitalized with documented infections uncommon to this patient population including Legionella pneumonia, Campylobacter bacteremia and fatal progressive multifocal leukoencephalopathy (PML). All patients received prior therapies for CLL/MCL. Immunological evaluation of these patients demonstrated immunoglobulin depression and profound lymphopenia with severe depletion in both B and CD4 T cell counts, suggesting defects in both humoral and T cell mediated immunity. This data support a broader immunosuppressive effect for ibrutinib than initially anticipated. While responding patients may show later recovery of B cell function, profound immunosuppression may occur at earlier treatment time points, particularly in previously treated patients. Closer patient monitoring during the first months of ibrutinib therapy may be desirable.

show abstract

“…In the ibrutinib phase 1b/2 study, five patients experienced VZV reactivation despite antiviral prophylaxis at some point in 85 out of 101 patients 6 ; subsequent reports confirm this 49 . Mild cases of PJP pneumonia identified predominantly by PCR were reported in 5 patients out of 96 receiving single agent ibrutinib, at a median of 6 months on therapy 50 . While PJP was clearly the cause of symptoms and related to ibrutinib, three of the patients did not immediately receive secondary prophylaxis and none recurred, leading the authors to suggest increased vigilance as opposed to universal prophylaxis 50 .…”

Section: Infections and Prophylaxis (Including Vaccines)mentioning

confidence: 99%

“…Mild cases of PJP pneumonia identified predominantly by PCR were reported in 5 patients out of 96 receiving single agent ibrutinib, at a median of 6 months on therapy 50 . While PJP was clearly the cause of symptoms and related to ibrutinib, three of the patients did not immediately receive secondary prophylaxis and none recurred, leading the authors to suggest increased vigilance as opposed to universal prophylaxis 50 . Even so, I have continued my practice to use prophylaxis for both VZV and PJP in any relapsed CLL patient on any therapy.…”

Section: Infections and Prophylaxis (Including Vaccines)mentioning

confidence: 99%

How I treat CLL patients with ibrutinib

Brown

2018

Blood

View full text Add to dashboard Cite

Ibrutinib is a transformative therapy for high-risk and relapsed refractory chronic lymphocytic leukemia (CLL) patients. In clinical trials in relatively healthy younger patients, ibrutinib has been well tolerated. As its use has become more widespread in the community, however, its full adverse event profile has emerged and proven more challenging than was initially anticipated. Reports of community-based use have estimated discontinuation rates as high as 40% in the first year of therapy. This article therefore reviews my approach to the evaluation and management of a CLL patient starting on ibrutinib, with the goal of minimizing and managing toxicity to maintain patients on ibrutinib. Key topics discussed include bleeding risk; cardiac complications, particularly atrial fibrillation; drug interactions; and infections.

show abstract

Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib

Abstract: Key Points Treatment with single-agent ibrutinib can increase susceptibility to PCP in chronic lymphocytic leukemia patients. Key components of PCP diagnosis are increased clinical suspicion and adequate sampling with diagnostic bronchoscopy.

Cited by 152 publications

References 20 publications

Optimising outcomes for patients with chronic lymphocytic leukaemia on ibrutinib therapy: European recommendations for clinical practice

Optimising outcomes for patients with chronic lymphocytic leukaemia on ibrutinib therapy: European recommendations for clinical practice

Atypical Infections in Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma Patients Treated with Ibrutinib

How I treat CLL patients with ibrutinib

Contact Info

Product

Resources

About