BJH - volume 6, issue 5, december 2015
A. Janssens MD, PhD
The first-in-class Bruton’s tyrosine kinase and phosphatidylinositol-3-kinase delta inhibitors have demonstrated impressive clinical activity and tolerability in several B-cell malignancies, both as single agent or in combination with rituximab. As reimbursement of ibrutinib and idelalisib by the Belgian national public health insurance has been granted, this review describes mechanism of action, dosage and administration, efficacy and tolerability. Although both molecules show a very favourable toxicity profile, treating physicians and patients must be aware of some medical events of interest.
(BELG J HEMATOL 2015;6(5):216–24)
Read moreBJH - volume 6, issue 5, december 2015
K. Fostier MD, R. Schots MD, PhD
Monoclonal antibodies have a profound impact on the prognosis and survival of patients with haematological malignancies. In the treatment of multiple myeloma, until recently, results of monoclonal antibodies have been disappointing. The introduction of two novel classes of monoclonal antibodies holds great promise to change this. Daratumumab (and related antibodies) is a monoclonal antibody directed to CD38, an intriguing multifunctional surface protein abundantly expressed on malignant plasma cells and their precursors. Daratumumab displays impressive single agent activity in heavily pretreated multiple myeloma patients and due to its favourable safety profile, this molecule seems to be an excellent accessory companion to known anti-multiple myeloma regimens and also in monotherapy as a maintenance agent. Elotuzumab, to the contrary, is an anti-CS1 monoclonal antibody, which does not show any clinically relevant single agent activity, but when combined with other anti-multiple myeloma drugs appears to greatly enhance their efficacy and can even revert the refractory state to the agents. When these promising results are confirmed in phase III trials, immunotherapy can finally be incorporated in the treatment schedule of newly diagnosed and relapsed/refractory multiple myeloma patients.
(BELG J HEMATOL 2015;6(5):209–15)
Read moreBJH - volume 6, issue 4, october 2015
D. Bron MD, PhD, M. Maerevoet MD
Phosphoinositide 3-kinase inhibitors represent a new group of promising targeted therapies for malignant hemopathies and primarily lymphoproliferative disorders. This short report summarises recent knowledge on the mechanism of action, the rationale to use it in humans bearing malignant hemopathies and preliminary clinical trials’ data that led to the Food and Drug Administration approval of one of these compounds (idelalisib).
(BELG J HEMATOL 2015;6(4): 152–5)
Read moreBJH - 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
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)
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