Serosal inflammation (pleural and pericardial effusions) related to tyrosine kinase inhibitors

Abstract

Tyrosine kinase inhibitors (TKIs) have dramatically changed the treatment of chronic myeloid leukemia (CML) and are increasingly used in other malignancies. Despite the apparent selectivity of these agents significant side effects can occur mainly due to off target kinase inhibition. Clinical consequences of serosal inflammation, including pleural and pericardial effusions, have emerged as a frequent adverse event associated with dasatinib while occurring much less frequently during imatinib and nilotinib therapy. The pathogenesis is uncertain but may involve inhibition of platelet derived growth factor or expansion of cytotoxic T and natural killer cells. The development of serosal inflammation with dasatinib poses a significant challenge to physicians, as it cannot be predicted, the time of onset is variable, and management frequently requires repeat invasive procedures.

Extensive pleural and pericardial effusion in chronic myeloid leukemia during treatment with dasatinib at 100 mg or 50 mg daily

“…[6][7][8][9][10]12,13 This side-effect has also been referred to as serosal inflammation and apparently develops more commonly in patients with advanced disease. 16,17 In initial reports, the incidence of grade III or IV pleural effusions was reported to be rather low. On the other hand, effusion formation accumulates over time.…”

“…Most likely, several different factors contribute to effusion formation. 16,18 An interesting aspect is that dasatinib binds to and blocks major kinases of the immune system including Lyn, Btk, and Src, with consecutive deactivation of immune cells. 11,13,15 At low concentration, however, dasatinib may even trigger the activation of certain immune cells.…”

Chronic GvHD-associated serositis and pericarditis

“…11 patients died during the period of follow-up, with four ultimately dying directly from or as a consequence of chronic GvHD. Other causes of death included pneumonia (1), hemorrhagic pericarditis (1), multiorgan failure (2), myocardial infarction (1) and relapsed cancer (2). Of those who died as a consequence of chronic GvHD, three deaths occurred during their hospitalization for pericarditis, either as a direct consequence of the pericarditis or from inability to control GvHD-related symptoms.…”

“…It is defined as inflammation of any of the serosal linings of the body, including the pleura, peritoneum and pericardium. 1 In the non-transplant setting, serosal inflammation can be caused by many different factors, including drugs, 2 infections, [3][4][5] exposure to ionizing radiation, 6,7 hereditary conditions, 8,9 autoimmune disorders 10 and malignant disease. [11][12][13] In the hematopoietic cell transplant (HCT) setting, serositis and pericardial effusions are seen as an 'other' manifestation in patients with established cGvHD and even in this setting attributing them to cGvHD is a diagnosis of exclusion.…”

Cardiac tamponade in a patient treated by sunitinib for metastatic renal cell carcinoma

“…Sunitinib also inhibits multiple receptor tyrosine kinases including platelet derived growth factor B (PDGFR B) which has a special function in angiogenesis and maintenance of tissue interstitial fluid pressure. Thus, inhibition of PDGFR B by sunitinib may contribute to increased risk of pericardial effusion (10). Besides, hypersensitivity or immune-mediated reaction to sunitinib rather than fluid reaction, as seen in other TKI-treated cases may be the reason of pericardial effusion (6).…”