BJH - volume 10, issue 8, december 2019
J. Blokken PhD, PharmD, T. Feys MBA, MSc
Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with biologically active cytotoxic molecules or drugs. As such, they can deliver cytotoxic agents specifically at the tumour site in a way that minimises systemic exposure and its associated toxicity. As of 2001, four ADCs have been approved by the European Medicines Agency for multiple human malignancies: gemtuzumab ozogamicin, brentuximab vedotin, trastuzumab emtansine, and inotuzumab ozogamicin. In addition to this, several new promising agents are under development. Although ADCs represent a new, effective class of therapeutics, the selection of the appropriate cytotoxin and linker remains challenging and systemic toxicity and rapid clearance should be monitored carefully. This review gives an overview on the safety and efficacy of ADCs in the treatment of haematological malignancies.
(BELG J HEMATOL 2019;10(8):311–9)
Read moreBJH - volume 10, issue 8, december 2019
T. Feys MBA, MSc, J. Blokken PhD, PharmD
Bispecific T-cell engagers (BiTEs) are a class of immunotherapeutics that can redirect T cells to haematological malignancies. A key advantage of BiTEs over adoptive T-cell therapies, consists of the fact that a BiTE is an “off the shelf” meaning that the same product can be given to all patients. In contrast, adoptive T-cell therapies must be made from cells taken from each patient and as a result this strategy is more time consuming and potentially more expensive. The most successful BiTE to date is blinatumomab. This agent is made up of CD3 and CD19 single-chain variable regions linked by a glycine–serine linker. It binds selectively to CD3 expressing T cells and CD19 expressing B cells, leading to the formation of immune synapses between T cells and B cells. In doing so, blinatumomab redirects unstimulated cytotoxic T cells to specifically target and lyse CD19-positive B cells. Blinatumomab is currently approved for patients with relapsed/refractory and minimal residual disease positive B-cell precursor acute lymphoblastic leukaemia (B-ALL). This review will discuss the pivotal trials with this agent and will touch upon some of the additional BiTEs that are under clinical evaluation in haematological malignancies. Finally, some remaining challenges with respect to optimising the efficacy and safety of BiTEs will be addressed.
(BELG J HEMATOL 2019;10(8):332–8)
Read moreBJH - volume 10, issue 6, october 2019
J. Blokken PhD, PharmD
On Saturday, May 25th 2019, the Belgian Hematology Society (BHS) organised the first BHS patient network meeting in Brussels. Patients with lymphoma, chronic and acute leukaemia, myeloma, sickle cell disease and myeloproliferative neoplasms, their family members and friends were all welcome. The goal of this symposium was to discuss the role of patient organisations, summarise the latest advances in treatment of the different haematological malignancies and address the affordability of health care and the role of the government. Professor Rik Schots, head of the clinical haematology department at Brussels University Hospital, introduced the patients to haematology and the work of the BHS.
(BELG J HEMATOL 2019;10(6):255–7)
Read moreBJH - volume 10, issue 5, september 2019
J. Blokken PhD, PharmD
In addition to the long list of abstracts dedicated to malignant haematology, EHA 2019 also featured several sessions dedicated to benign haematological abnormalities. Results from the Northstar clinical trial program highlighted the efficacy of LentiGlobin gene therapy in transfusion-dependant β-thalassaemia. The BELIEVE study showed that Luspatercept treatment was associated with increased HbF in patients with red blood cell (RBC) transfusion dependent (TD) β-thalassaemia in both responders and non-responders. With respect to paroxysmal nocturnal haemoglobinuria, ravulizumab (a novel C5 complement inhibitor) and ACH-4471 (an inhibitor of factorD, a highly specific serine protease that cleaves factor B) proved to be promising new drugs. Finally, long term inhibition of complement C1s with the humanized monoclonal antibody sutimlimab can be a new strategy in treating patients with cold agglutinin disease.
(BELG J HEMATOL 2019;10(5):220–3)
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