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, PhD, M. André MD, PhD, C. Hermans MD, PhD, A. Janssens MD, PhD
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)
Read moreBJH - volume 12, issue 3, may 2021
A. Janssens MD, PhD, D. Selleslag MD, J. Depaus MD, Y. Beguin MD, PhD, C. Lambert MD, PhD
The Belgian Hematology Society (BHS) updated the 2013 guidelines for diagnosis and treatment of primary immune thrombocytopenia (ITP).1 As knowledge about ITP pathophysiology is increasing, the mode of action of old therapies is better understood and novel drugs are introduced to target more specific pathways. Corticosteroids with or without intravenous immunoglobulins (IgIV) remain the first line treatment. According to the updated international guidelines, a short course of corticosteroids rather than a prolonged treatment has to be recommended. The same guidelines stress that consequent therapies as thrombopoietic agents (TPO-RAs) and rituximab should be available independent of duration of ITP. Although the majority of recommendations is based on very low-quality evidence, it is strongly advised to individualise the ITP management taking patient values and preferences in account. The main treatment goal in all ITP patients must be to maintain a safe platelet count to prevent or stop bleeding with a minimum of toxicity and not to normalise the platelet count.
(BELG J HEMATOL 2020;12(3):112-27)
Read moreBJH - volume 12, issue 3, may 2021
A. Janssens MD, PhD, L. Stas MSc, M. Van den Enden MD, E. Van den Neste MD, PhD
Chronic lymphocytic leukaemia (CLL) is a slow-progressing cancer that results in uncontrolled proliferation and accumulation of B-lymphocytes in the blood and bone marrow and is the most common form of leukaemia in the western world. CLL patients harbouring a deletion of chromosome 17 (del17p) or the TP53 mutation, who progress after treatment with immunological, chemotherapeutic as well as targeted agents such as ibrutinib have poor prognosis signifying a population with an unmet medical need. Clinical studies showed that venetoclax, a selective; orally bioavailable Bcl-2 inhibitor, induces CLL cell apoptosis, and offers an alternative therapeutic option for CLL, either as a monotherapy or in combination with rituximab. BRAVe was a multicentre, observational retrospective study, conducted in Belgium. The main objectives of this study were to evaluate the safety and effectiveness of venetoclax monotherapy in Belgian patients with CLL, as well as the utilisation of resources in a real life setting. The results show a manageable/favourable safety profile for venetoclax with limited burden for patients and sites, and a good overall response rate in pre-treated CLL patients in the relapsed/refractory setting.
(BELG J HEMATOL 2020;12(3):106-11)
Read moreBJH - volume 12, issue 1, february 2021
A. Janssens MD, PhD
Our recent BHS guidelines for the management of small lymphocytic lymphoma (SLL) and chronic lymphocytic leukaemia (CLL) made by the BHS lymphoproliferative disease committee are not challenged after ASH 2020. One educational session discussed “chemotherapy-free frontline therapy for CLL” and “standard approaches for the relapsed/refractory (R/R) CLL after chemoimmunotherapy (CIT) or novel agents”. Managing toxicities of targeted therapies (BTKi, Pi3Ki, and venetoclax) was the topic of another educational session. Andrew Roberts highlighted the importance of bcl-2 inhibition in CLL and other hematological malignancies in the Ham-Wasserman session.
(BELG J HEMATOL 2021;12(1):25-8)
Read moreBJH - volume 11, issue 7, november 2020
J. Loos MD, M. Beckers MD, PhD, V. Beckers MD, M. Hoyoux MD, prof. dr. W. Peetermans MD, PhD, A. Van De Velde MD, PhD, V. Van Hende MD, A. Vanderfaeillie MD, Y. Van Laethem MD, PhD, A. Janssens MD, PhD
Patients with hematological malignancies suffer from widely varying degrees of immunodeficiency, which leads to an increased susceptibility to a wide range of infections. Some of these, such as influenza and invasive pneumococcal disease, are vaccine preventable. During the Covid19 pandemic these past months patients with hematological malignancies have already shown to be at greater risk of dying, with mortality rates of up to 30% in hospitalized patients.1,2 This has once again highlighted the importance of robust and widely spread vaccination strategies, also we eagerly await an available vaccine for Covid19. In this review, the advisory board on vaccination of the Belgian Hematological Society (BHS), consisting of experts from various disease committees as well as two infectious disease experts attempts to provide clear recommendations regarding vaccinations in patients with hematological malignancies and asplenia. Although transplant recipients share many of the immunodeficiencies of those not transplanted, clear guidelines and vaccination schedules have already been published.3
(BELG J HEMATOL 2020;11(7):305-316)
Read moreBJH - volume 11, issue 5, september 2020
A. Janssens MD, PhD
We refer to the recent Belgian Haematological Society (BHS) guidelines for the management of small lymphocytic lymphoma (SLL) and chronic lymphocytic leukaemia (CLL) made by the BHS lymphoproliferative disease committee. The 2020 publication is already the third update after the initial paper published in 2012. For diagnosing CLL, we recommend using the immunophenotype panel according the European research initiative on CLL and European society for clinical cell analysis (ERIC/ESCCA) harmonization project. Concerning diagnostic and pre-treatment work-up, we advise testing of the IGVH mutational status only in young ‘and’ older patients without a 17p del/TP53 mutation if chemo-immunotherapy (CIT) could be a therapeutic option. We are waiting for reimbursement of the IGVH testing in this small number of elderly patients. The recently updated international workshop on CLL (iwCLL) guidelines added as indication for initiating treatment ‘symptomatic functional extranodal disease’. Although criteria for initiating first-line or second-line treatment follow in general similar rules, the same iwCLL guidelines stress that subsequent therapy can be acceptable, sometimes in overlap with the previous one, in patients when substantial disease persists or disease progresses under novel agents, even if the patient stays asymptomatic, to avoid Richter-like acceleration.1 At EHA 2020, an update on treatment advances in previously untreated and relapsed/refractory CLL was given. This overview will provide an update on the most important study results and how these results might change the current guidelines in the treatment of CLL.
(BELG J HEMATOL 2020;11(5):209-15)
Read moreBJH - volume 11, issue 4, june 2020
A. Janssens MD, PhD, D. Bron MD, PhD, V. Van Hende MD, V. Galle MD, K. Jochmans MD, PhD, S. Meers MD, PhD, M. André MD, PhD, M-C. Ngirabacu MD, PhD, K.L. Wu MD, PhD, B. De Prijck MD, P. Verhamme MD, PhD, C. Hermans MD, PhD
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)
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