BJH - volume 14, issue 2, march 2023
J. Brijs MD, J. Neefs PharmD, A. Janssens MD, PhD
Lymphomas are the most common haematological malignancy and represent a heterogenous group of lymphoproliferative diseases with a variable prognosis. Chemotherapy and radiotherapy, and anti-CD20 immunotherapy for B-cell lymphomas, currently form the basis of lymphoma treatment. New agents, especially new forms of cancer immunotherapy, such as bispecific antibodies (bsAbs), have expanded therapeutic approaches in the last years. bsAbs have two different antigen binding sites, which enables them to simultaneously target tumour cells and immune effector cells (T-cells). By binding and activating T-cells in the proximity of tumour cells, an effective T-cell mediated anti-tumour response can be achieved. Target antigens in lymphomas are mostly CD19 or CD20 on the malignant B-cell and CD3 on the T-cell. This article will briefly review the basic principles and mechanisms of action of bsAbs, discuss the molecules approved or in advanced clinical development for lymphomas with their most relevant (dose-escalation/dose-expansion) trials, and pay attention to possible adverse events and future perspectives of bsAbs.
(BELG J HEMATOL 2023;14(2):67–72)Read more
BJH - volume 13, issue 6, october 2022
D. Mazure MD
Despite the success of tyrosine kinase inhibitors in the treatment of chronic myeloid leukaemia, there are some patients who fail these drugs because of intolerance or lack of efficacy. Asciminib is a first-in-class STAMP-inhibitor (Specifically Targeting the ABL Myristoyl Pocket) and has a different mode of action as the classical tyrosine kinase inhibitors. Clinical trials, most recently the phase III ASCEMBL trial, show clinical activity in heavily pre-treated patients with an acceptable safety profile. Asciminib therefore forms a promising treatment option for those patients failing the currently available drugs.
(BELG J HEMATOL 2022;13(6):243–8)Read more
BJH - volume 13, issue 4, june 2022
T. Van Nieuwenhuyse PharmD, A. Janssens MD, PhD
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)Read more
BJH - volume 13, issue 3, may 2022
D.A. Breems MD, PhD
With the publication of improved survival results of previously untreated patients with acute myeloid leukaemia ineligible for intensive chemotherapy treated with the combination of venetoclax and a hypomethylating agent, the treatment paradigm for patients with AML has been changed. This paper discusses the past, present and future of AML therapy with venetoclax.
(BELG J HEMATOL 2022;13(3):124–7)Read more
BJH - volume 13, issue 2, march 2022
M. Vercruyssen MD
Multiple myeloma is the second most common haematological cancer in adults, reaching 1.8% of all neoplasms. Despite a dramatic improvement in the treatment, multiple myeloma is still an incurable disease with a median overall survival of five years. Therefore, new therapeutic approaches are needed to further improve outcomes, especially for high-risk myeloma that are often refractory, rapidly relapsing, and/or harbouring more aggressive features. Bispecific antibodies simultaneously target tumour cells and patient’s own effector immune cells, activating the latter close to the former leading to the killing of myeloma cells. Various targets on myeloma cells have been selected and are now part of clinical trials with very promising results. This review reports the latest data of the main ongoing studies and proposes a place for this new treatment in the large armamentarium against multiple myeloma.
(BELG J HEMATOL 2022;13(2):81–3)Read more
BJH - volume 12, issue 8, december 2021
M. Beckers MD, PhD
Luspatercept, a first-in-class erythroid maturation agent is approved by the European Medicine Agency (EMA) for the treatment of adult patients with transfusion-dependent anaemia due to very low, low and intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts, who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy. Luspatercept showed promising activity for treating anaemia in lower risk myelodysplastic syndrome with ring sideroblasts. Both the PACE and MEDALIST trial showed high rates of durable red blood cell transfusion independence and hematological improvement with luspatercept and a manageable toxicity profile.
(BELG J HEMATOL 2021;12(8):344–8)Read more
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 more