PHARMACOTHERAPY

The role of venetoclax in the current treatment paradigm for patients with acute myeloid leukaemia

BJH - volume 13, issue 3, may 2022

D.A. Breems MD, PhD

SUMMARY

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)

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Bispecific antibodies: New hope in multiple myeloma

BJH - volume 13, issue 2, march 2022

M. Vercruyssen MD

SUMMARY

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)

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A new kid on the block: Luspatercept in low-risk myelodysplastic syndrome

BJH - volume 12, issue 8, december 2021

M. Beckers MD, PhD

SUMMARY

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)

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Ibrutinib and atrial fibrillation: A Belgian expert consensus paper

BJH - volume 12, issue 4, june 2021

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

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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CAR-T cells: new developments and implications in multiple myeloma

BJH - volume 12, issue 3, may 2021

M. Delforge MD, PhD, Y. Serroukh MD, PhD

SUMMARY

Despite significant progress in management of multiple myeloma (MM), prognosis of patients who fail standard treatment options is dismal. Therefore, refractory MM remains an unmet medical need. CAR-T cells are a form of cellular immunotherapy redirecting autologous T cells against tumour antigens after in vitro manufacturing. B-cell maturation antigen (BCMA) is the most promising target antigen for the development of CAR-T cell therapy for MM. In this review, we briefly go through the basics of CAR-T cell therapy applied to MM. We present the results on efficacy and safety of two recently developed CAR-T cell products: idecabtagene vicleucel (ide-cel or bb2121) and ciltacabtagene autoleucel (cilta-cel or JNJ-4528) and put them in perspective with what is published for approved CD19-CAR-T cells.

(BELG J HEMATOL 2020;12(3):128-31)

 

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CAR-T cells: New developments and implications in lymphoma

BJH - 2021, issue 2, march 2021

A. Bosly MD, PhD, E. Collinge MD, G. Crochet MD, H. Vellemans MD, M. André MD, PhD

SUMMARY

Recently, the use of chimeric antigen receptor modified T cells or CAR-T cells has emerged in the therapeutic arsenal of several hematological pathologies, including lymphoma. These CAR-T cells are the product of extensive research on understanding the mechanisms of tumour immunity and are the product of cellular engineering. By combining the specific recognition of an antibody and the activation pathways of a cytotoxic cell, CAR-T cells allow promising clinical results, but they also see the occurrence of side effects that are more specific to these treatments, which it is essential to manage in a multidisciplinary team. Different CAR-T cells are currently available, particularly in diffuse large cell B lymphoma. The trials that have enabled their use differ on many points, including patient selection, the manufacture of the CAR or the pre-therapeutic conditioning. In the future, the use of this expensive therapy could be extended to other lymphomas and new generations of CAR-T cells could emerge.

(BELG J HEMATOL 2020;12(2):77-84)

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Caplacizumab, a game changer in the treatment of acquired thrombotic thrombocytopenic purpura

BJH - volume 11, issue 3, may 2020

A. De Becker MD, N. De Beule MD, PhD, R. Schots MD, PhD

SUMMARY

Acquired or immune-mediated thrombotic thrombocytopenic purpura (aTTP) is a life-threatening auto-immune disorder caused by a functional deficiency of the von Willebrand factor-cleaving protease ADAMTS13, leading to thrombotic microangiopathy. The introduction of plasma-exchange has reduced mortality from over 90% to 10–20%. However, over the last two decades the treatment outcomes have not changed substantially. Caplacizumab, a humanised nanobody directed to the A1 domain of VWF, inhibits this lethal thrombotic cascade and is therefore essential for symptom control and prevention of irreversible end-organ damage. Both TITAN and HERCULES trials demonstrated that treatment with caplacizumab significantly reduced mean duration of hospitalisation and number of days of plasma-exchange. Moreover, no deaths were observed in caplacizumab-treated patients. Therefore, we can state that caplacizumab has changed the treatment paradigm of aTTP.

(BELG J HEMATOL 2020;11(3):120–7)

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