2.4.2 BCR-Abl inhibitors
All BCR-Abl (breakpoint cluster region and Abelson) inhibitors are
associated with peripheral edema (García-Gutiérrez & Hernández-Boluda,
2019) and serous effusions (García-Gutiérrez & Hernández-Boluda, 2019;
Rizzo et al., 2015). The risk of peripheral edema is greater with
imatinib and dasatinib both in terms of incidence (e.g., periorbital
and/or extremity edema in 74-84% imatinib-treated patients (Kim et al.,
2015)) and in terms of severity where they are grade 3/4 in 5-10% of
patients (García-Gutiérrez & Hernández-Boluda, 2019). The precise
molecular substrate remains elusive but could be related to both
on-target effects on endothelial Abl kinases (affecting vascular
permeability and cell-cell junction dynamics) (Rizzo et al., 2015) and
off-target inhibitory effects (e.g., Src kinases, platelet-derived
growth factor receptors) (Giles et al., 2009). Both Src kinases and
platelet-derived growth factor receptors regulate vascular permeability;
the latter also affecting interstitial hydrostatic pressure (Giles et
al., 2009). Imatinib has been shown to induce CLS (Hinchcliff, Lomasney,
Johnson, & Varga, 2016; Jeong et al., 2019). Pathophysiology involves a
decrease in the oncotic reflection coefficient through the capillary
wall. It is thought to be due to an endothelial dysfunction and
weakening of endothelial cell-to-cell binding secondary to
hypercytokinemia, resulting in rapid extravasation of albumin into the
extravascular space (Druey & Parikh, 2017; Siddall et al.,
2017).
Because of its uncertain pathogenesis, the management of drug-induced
CLS remains largely empiric and mainly based on drug discontinuation and
corticosteroids therapy to reduce cytokine release (Siddall et al.,
2017). Surprisingly, recent data suggest a potential benefit of imatinib
in certain forms of capillary hyperpermeability syndromes, including
Clarkson disease (Rizzo et al., 2015).