Articles

Acalabrutinib, a next-generation Bruton’s tyrosine kinase inhibitor

BJH - volume 13, issue 4, june 2022

T. Van Nieuwenhuyse PharmD, A. Janssens MD, PhD

SUMMARY

Bruton’s tyrosine kinase (BTK) inhibitors have demonstrated impressive clinical activity and tolerability in several B-cell malignancies, both as single agent or in combination with anti-CD20 monoclonal antibodies. Acalabrutinib, a next-generation BTK inhibitor, has been reimbursed recently by the Belgian national public health insurance for the treatment of chronic lymphocytic leukaemia (CLL). This review describes mechanism of action, dosage and administration, efficacy, and tolerability.

(BELG J HEMATOL 2022;13(4):156–64)

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Ibrutinib and atrial fibrillation: A Belgian expert consensus paper

BJH - volume 12, issue 4, june 2021

C. Vandenbriele MD, PhD, L. Van der Linden PhD, PharmD, L.N.L. Van Aelst MD, PhD, B. Schwagten MD, PhD, F. van Heuverswyn MD, S. Meers MD, PhD, V. Galle MD, T. Van Nieuwenhuyse PharmD, K.L. Wu MD, M. André MD, PhD, C. Hermans MD, PhD, A. Janssens MD, PhD

SUMMARY

Over the last decade, the oral Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib induced a paradigm shift in the treatment of patients with chronic lymphocytic leukaemia (CLL), mantle cell lymphoma (MCL), and Waldenströms macroglobulinemia (WM). In clinical trials and in real-world studies, ibrutinib proved to be an effective agent with an overall favourable safety and tolerability profile. However, compared with standard chemo-immunotherapy (CIT), ibrutinib was associated with a higher incidence of atrial fibrillation (AF). The patho-physiological mechanisms underlying this increased AF incidence are not completely understood, but it is thought to be related to off-target inhibitory effects of ibrutinib on the Tec protein tyrosine kinase (TEC) in cardiac cells. The prevalence of AF in patients treated with ibrutinib is highest during the first three months of therapy, which warrants an increased vigilance during this treatment phase. However, AF in patients treated with ibrutinib is generally well manageable without ibrutinib discontinuation. Prior to the start of ibrutinib treatment, identification and addressing modifiable risk factors for AF is a first important step. The threshold for haematologists to consult a cardiologist or a cardio-oncologist should be low and a close collaboration between both specialties is warranted. Unnecessary ibrutinib interruptions should be avoided, and uncomplicated AF is not a valid reason to discontinue or interrupt ibrutinib. If anticoagulation is required, direct oral anticoagulants are preferred. In this paper, a panel of haematology and cardiology specialists have provided practical guidance on how to evaluate patients prior to ibrutinib treatment and monitor during ibrutinib therapy. Furthermore, they have provided practical guidance on how to manage AF in ibrutinib-treated patients.

(BELG J HEMATOL 2021;12(4):155-64)

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