BJH - volume 6, issue 2, may 2015
J. Van Droogenbroeck MD
More than ten years ago the dipeptidyl boronic acid derivative proteasome inhibitor bortezomib changed the therapeutic field of multiple myeloma dramatically. This introduction of a whole new class of chemotherapy lead to a significant extension of disease-free and overall survival for most myeloma patients. But as with most first-in-class molecules, efficacy can probably be improved — primary and secondary bortezomib resistance being common – and treatment is all too often limited by dose-limiting side effects.2 Carfilzomib is without doubt a very promising next generation proteasome inhibitor.
(BELG J HEMATOL 2015;6(2):71–3)
Read moreBJH - volume 5, issue 4, december 2014
C. Doyen MD, PhD
Relapsed and refractory multiple myeloma patients have a particularly poor prognosis and the development of new drugs is urgently needed. Pomalidomide, a third-generation immunomodulatory drug with a pleiotropic activity, was approved in 2013 by the Food and Drug Administration and the European Medicines Agency, in association with low dose dexamethasone in relapsed and refractory multiple myeloma, in patients who received at least two prior therapies, including bortezomib and lenalidomide and demonstrated progression on the last therapy. In the phase III MM-003 study, pomalidomide associated with low dose dexamethasone was superior to high dose dexamethasone in these patients, with a manageable safety and tolerability profile. This paper will review the available data concerning the mechanisms of action, the efficacy in clinical studies and the safety of this very promising new drug.
(BELG J HEMATOL 2014;5(4):137–42)
Read moreBJH - volume 5, issue 3, september 2014
A. Janssens MD, PhD
Bendamustine is an efficacious treatment for several lymphoma subtypes with a mild toxicity profile. This review will describe practical recommendations concerning administration and adverse events to guide the clinician in the optimal use of this compound.
(BELG J HEMATOL 2014;5(3):97–103)
Read moreBJH - volume 5, issue 2, june 2014
M. Delforge MD, PhD
During the last decade, thalidomide, lenalidomide and bortezomib have significantly improved the outcome for patients with multiple myeloma. Although still frequently referred to as ‘novel agents’, a newer generation of more potent proteasome inhibitors and immunomodulatory drugs are expected to enter the myeloma clinic in the near future. New proteasome inhibitors like carfilzomib have shown unprecedented anti-myeloma activity, particularly when combined with lenalidomide and dexamethasone. Other proteasome inhibitors under development will be more patient-friendly by becoming orally available. In the class of immunomodulatory drugs, it is expected that pomalidomide will be registered in the near future for refractory myeloma patients, based on convincing phase III data. Finally, after many years of research, myeloma also has its monoclonal antibodies. Daratumumab and elotuzumab are evaluated in several clinical studies. All these new agents will not replace the current, yet not old, anti-myeloma drugs. The major challenge will become to prove that optimal drug sequencing or combination, guided by science and clinical experience, will continue to prolong the life expectancy of patients with multiple myeloma.
(BELG J HEMATOL 2014;5(2):55–9)
Read moreBJH - volume 4, issue 4, december 2013
T. Bauters PharmD, PhD, V. Mondelaers MD, B. De Moerloose MD, PhD, H. Robays PharmD, Y Benoit MD, PhD
PEG-L-Asparaginase (Oncaspar®) is a major compound of antineoplastic combination therapy for reinduction in acute lymphoblastic leukaemia in children and adults with known hypersensitivity. In the United States, it has been approved for many years as first-line treatment of children with acute lymphoblastic leukaemia. Its clinical benefits have been extensively described. In this report, a cost-minimisation analysis comparing the direct cost of PEG-L-asparaginase with that of native E. coli and Erwinia L-asparaginase treatment is described.
(BELG J HEMATOL 2013; 4(4): 144–147)
Read moreBJH - volume 4, issue 4, december 2013
V. Mondelaers MD, T. Bauters PharmD, PhD, B. De Moerloose MD, PhD, Y Benoit MD, PhD
Asparaginase is an essential compound of combination chemotherapy in acute lymphoblastic leukaemia in children and adults. Essentially, three preparations of asparaginase are used in childhood acute lymphoblastic leukaemia: native Escherichia coli asparaginase, Erwinia chrysanthemi asparaginase and PEG-asparaginase. Although PEG-asparaginase seems to have some advantages over the other asparaginase preparations, its clinical use in Europe is limited to second-line therapy after allergic reactions to native asparaginase. This is in contrast to the United States, where PEG-asparaginase has been approved as first-line treatment of children with acute lymphoblastic leukaemia. This report describes the properties, clinical benefits and side effects of PEG-asparaginase.
(BELG J HEMATOL 2013;4(4): 138–143)
Read moreBJH - volume 4, issue 3, september 2013
D. Bron MD, PhD
The Bruton’s tyrosine kinase protein is expressed in most hematopoietic cells with the exception of T cells and natural killer cells, but the selective effect of Bruton’s tyrosine kinase mutations suggests that its primary functional role is in antigen receptor signalling in B cells. Ibrutinib (=PCI-32765) was designed as a selective and irreversible inhibitor of the Bruton’s tyrosine kinase protein. In vitro, PCI-32765 arrested cell growth and induced apoptosis in human B-cell lymphoma cell lines, and inhibited tumour growth in vivo in xenograft models. A first analysis performed on 116 naive chronic lymphocytic leukaemia patients with a median age of 71 (range: 65 – 84) shows an estimated 22-months progression-free survival rate of 96%; the median progression-free survival or overall survival had not been reached.1 In 61 patients with relapsed/ refractory chronic lymphocytic leukaemia/small lymphocytic lymphoma with a median age of 64 years (range: 40 – 81) and a high-risk cohort (24 patients), the estimated 22-months progression-free survival rate for the 85 relapse/refractory and high-risk patients was 76%. PCI-32765 (ibrutinib) has demonstrated promising activity in studies enrolling older patients with treatment-naive or relapsed/refractory chronic lymphocytic leukaemia and older patients with small lymphocytic lymphoma. Randomised phase III studies in naïve chronic lymphocytic leukaemia/small lymphocytic lymphoma patients are currently on-going.
(BELG J HEMATOL 2013;4(3): 102–105)
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