Dasatinib-Induced Pleural Effusions: A Lymphatic Network Disorder?

Goldblatt, Mark R.; Huggins, John T.; Doelken, Peter; Gurung, Puncho; Sahn, Steven A.

doi:10.1097/maj.0b013e3181ae9227

Cited by 34 publications

(24 citation statements)

References 13 publications

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“…14 -18 One of the common nonhematologic side effects of dasatinib is fluid retention and pleural effusions, but the underlying mechanisms remain unclear. [11][12][13] Interestingly, we observed bilateral pleural effusions in 6 patients; however, severe precapillary PH persisted even after resolution of pleural effusions. Although PH remains a rare complication, it is important to note that, at this time, dasatinib was licensed only as a second-line therapy.…”

Section: Discussionmentioning

confidence: 91%

“…10 Pulmonary complications, and specifically pleural effusions, have been reported more frequently with dasatinib use compared with other TKIs. [11][12][13] In addition, some case reports have suggested that PH may be a potential specific complication of dasatinib use. 14 -19 By contrast, clinical and hemodynamic improvements have been reported with imatinib therapy in 2 patients with CML and coexistent severe precapillary PH.…”

Section: Editorial See P 2057 Clinical Perspective On P 2137mentioning

confidence: 99%

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Pulmonary Arterial Hypertension in Patients Treated by Dasatinib

et al. 2012

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Background-The French pulmonary hypertension (PH) registry allows the survey of epidemiological trends. Isolated cases of precapillary PH have been reported in patients who have chronic myelogenous leukemia treated with the tyrosine kinase inhibitor dasatinib. Methods and Results-This study was designed to describe incident cases of dasatinib-associated PH reported in the French PH registry. From the approval of dasatinib (November 2006) to September 30, 2010, 9 incident cases treated by dasatinib at the time of PH diagnosis were identified. At diagnosis, patients had moderate to severe precapillary PH with functional and hemodynamic impairment. No other incident PH cases were exposed to other tyrosine kinase inhibitors at the time of PH diagnosis. Clinical, functional, or hemodynamic improvements were observed within 4 months of dasatinib discontinuation in all but 1 patient. Three patients required PH treatment with endothelin receptor antagonist (nϭ2) or calcium channel blocker (nϭ1). After a median follow-up of 9 months (min-max 3-36), the majority of patients did not demonstrate complete clinical and hemodynamic recovery, and no patients reached a normal value of mean pulmonary artery pressure (Յ20 mm Hg). Two patients (22%) died at follow-up (1 of unexplained sudden death and 1 of cardiac failure in the context of septicemia, respectively, 8 and 12 months after dasatinib withdrawal). The lowest estimate of incident PH occurring in patients exposed to dasatinib in France was 0.45%. Conclusions-Dasatinib may induce severe precapillary PH fulfilling the criteria of pulmonary arterial hypertension, thus suggesting a direct and specific effect of dasatinib on pulmonary vessels. Improvement is usually observed after withdrawal of dasatinib. (Circulation. 2012;125:2128-2137.)

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Section: Discussionmentioning

confidence: 91%

Section: Editorial See P 2057 Clinical Perspective On P 2137mentioning

confidence: 99%

Pulmonary Arterial Hypertension in Patients Treated by Dasatinib

et al. 2012

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“…The pathogenesis of dasatinib-associated pleural effusion is unclear. The fact that pleural effusions consist in the vast majority of the cases in lymphocyte-predominant exudates with the presence of chyle argues against drug-induced fluid retention as an explanation of effusion formation and supports the hypothesis of a dysregulation of the lymphatic network [36,37]. Pleural effusions were observed in up to one third of imatinib-resistant CML patients during the first clinical evaluation in a phase I trial, and subsequent phase 2 studies in which the drug was evaluated at 70 mg BID confirmed these findings [38].…”

Section: Pulmonary Toxicitymentioning

confidence: 88%

Management of adverse events associated with tyrosine kinase inhibitors in chronic myeloid leukemia

Réa

2015

Ann Hematol

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Tyrosine kinase inhibitors (TKIs) targeting the breakpoint cluster region-Abelson 1 (BCR-ABL1) oncoprotein represent an outstanding progress in chronic myeloid leukemia (CML), and long-term survival has become a reality. However, the majority of patients need to be treated during their entire life span; thus, outcome does not solely depend on treatment efficacy but also on how well therapy is tolerated. TKIs have an overall favorable safety profile in clinical practice. Although many patients may encounter adverse events, these usually occur early after treatment initiation, are mild to moderate in intensity and resolve spontaneously, or are easily controlled with adequate supportive care. Whenever treatment interruption is necessary, re-exposition to the same TKI or switch to an alternative TKI is successful in the majority of the cases. However, long-term safety issues have not been fully elucidated at present, especially for new-generation TKIs. Recent evidence has emerged that these new agents may sometimes impinge on vital organs such as the heart and lung in an irreversible fashion especially when comorbidities are present; thus, decision regarding of which TKI should be used must take into account disease-related, TKI-related, and patient-related variables. The purpose of this article is to provide an up-to-date review of common adverse events associated with TKIs and how these events may be optimally managed.

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“…Until now, pulmonary side-effects, including pleural effusions and PAH, have been more frequently reported with dasatinib than with other TKIs. Indeed, dasatinib-induced exudative pleural effusion is a frequent adverse event ranging from 15% to 35% [2,3,[5][6][7]. Although the known incidence of bosutinib-induced pleural effusion is considered to be rare [8,9], we report two cases of exudative lymphocytic pleural effusions that rapidly regressed after bosutinib withdrawal.…”

mentioning

confidence: 87%

“…Pleural effusions and pulmonary arterial hypertension (PAH) have been reported in patients treated with these agents [2][3][4]. These side-effects are more frequently observed with dasatinib use, with partial or complete reversibility after drug withdrawal [3].…”

mentioning

confidence: 99%

Deterioration of pulmonary hypertension and pleural effusion with bosutinib following dasatinib lung toxicity

et al. 2016

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Tyrosine kinase inhibitors (TKIs) targeting BCR/ABL such as imatinib, nilotinib, dasatinib, bosutinib and ponatinib have revolutionised the management of patients with chronic myeloid leukaemia (CML) [1]. Pleural effusions and pulmonary arterial hypertension (PAH) have been reported in patients treated with these agents [2][3][4]. These side-effects are more frequently observed with dasatinib use, with partial or complete reversibility after drug withdrawal [3]. Bosutinib is a second-generation TKI prescribed in case of intolerance or resistance to imatinib, nilotinib or dasatinib. In the present report, we describe two cases of worsening of dasatinib-induced PAH and two cases of severe pleural effusions, suggesting overlapping pulmonary toxicity of bosutinib and dasatinib.Patient 1, a 44-year-old Caucasian woman with CML, was successively treated with hydroxycarbamide, imatinib, nilotinib and dasatinib. After 3 years on dasatinib, she complained of exertional dyspnoea, New York Heart Association functional class (NYHA FC) II. Echocardiography showed a dilated right ventricle and an estimated systolic pulmonary artery pressure (PAP) of 80 mmHg. Right heart catheterisation demonstrated pre-capillary pulmonary hypertension (mean PAP 34 mmHg, pulmonary capillary wedge pressure (PCWP) 9 mmHg, cardiac index (CI) 3.8 L·min

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Dasatinib-Induced Pleural Effusions: A Lymphatic Network Disorder?

Cited by 34 publications

References 13 publications

Pulmonary Arterial Hypertension in Patients Treated by Dasatinib

Pulmonary Arterial Hypertension in Patients Treated by Dasatinib

Management of adverse events associated with tyrosine kinase inhibitors in chronic myeloid leukemia

Deterioration of pulmonary hypertension and pleural effusion with bosutinib following dasatinib lung toxicity

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