K. Jochmans MD, PhD

Ibrutinib and bleeding management: a Belgian expert consensus

SUMMARY

In recent years ibrutinib emerged as a paradigm shifting agent in the treatment of chronic lymphocytic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström’s macroglobulinemia (WM). In clinical trials and in real-world studies ibrutinib proved to be an effective agent with an overall favourable tolerability profile. However, compared with standard chemo-immunotherapy (CIT), ibrutinib was associated with a higher incidence of clinically significant bleeding. This has been hypothesized to be linked to the platelet-specific effects of inhibiting Bruton’s tyrosine kinase (BTK). Most bleeding events under ibrutinib are low-grade with a decreasing incidence over time. However, bleeding can have a significant impact on patients and interfere with persistence and compliance of ibrutinib treatment. Currently, no clear consensus exists on the use of ibrutinib in patients with an increased bleeding risk, on the management of ibrutinib-induced bleeding and on the use of ibrutinib around surgery or invasive procedures. In this paper, a panel of Belgian haematology and haemostasis specialists formulated practical advice on bleeding prevention and management in ibrutinib-treated patients.

(BELG J HEMATOL 2020;11(4):174–84)

The role of direct oral anticoagulants in the management of cancer-associated thrombosis

Cancer patients are at an increased risk of venous thromboembolism (VTE). The current standard initial treatment of an acute episode of VTE in cancer patients consists of the administration of three to six months of subcutaneous low molecular weight heparin (LMWH) at a dose adjusted to the body weight. The efficacy and safety profile of LMWHs are well established, but a drawback of these agents is that they require daily subcutaneous administration. In addition, they are mainly cleared through the kidneys, and their use in patients with severe renal insufficiency may require dose reduction or monitoring of the anti-Xa activity. To address the issues with LMWH, several direct oral anticoagulants (DOAC) have been developed for the treatment of VTE. In contrast to LMWHs and vitamin K antagonist, DOACs directly interfere with thrombin or activated factor X (FXa). DOACs have now become standard treatment options in the general management of VTE, but until recently, there were no results of clinical trials specifically assessing the role of DOACs in the treatment of cancer-associated thrombosis. Recently, the Hokusai VTE cancer study and preliminary data from the Select-D trial demonstrated that DOACs are non-inferior to LMWH in preventing recurrent VTE. However, both studies also show that this comes at the cost of an increased rate of both major and clinically-relevant non-major bleeding. Especially in the subgroup of patients with gastrointestinal cancer, the benefit in VTE recurrence with the DOAC seems to be outbalanced by a significantly increased bleeding risk. Based on the available results, DOACs might represent an interesting alternative for LMWH in certain subgroups of patients, but with an important list of exceptions. It seems reasonable not to use DOACs in patients with a high bleeding risk, and especially in patients with gastrointestinal cancer, DOACs should not be the first-line choice. In summary, while LMWHs are currently the standard of care in the acute management of cancer-associated thrombosis, the advent of DOACs is welcomed for patients at a low bleeding risk who are in need of long-term anticoagulation.

(BELG J HEMATOL 2019;10(4):169–76)

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