C. Graux MD, PhD

Blinatumomab: beyond clinical trials

SUMMARY

Immunotherapy is an alternative treatment modality for poor conditions associated with chemoresistance like refractory/relapsing primary B-precursor acute lymphoblastic leukaemia or minimal residual disease persistence. The immunotherapeutic effect of allogeneic stem cell transplantation is largely exploited in this context but graft-versus-host disease remains a major concern. Recently, improvements have been made in selectively engaging the immune system against the persistent disease. Blinatumomab is a dual binding antibody construct that redirects any T lymphocytes against B-precursor acute lymphoblastic leukaemia blasts. It shows a very good activity in monotherapy in those poor risk conditions and is associated with a low toxicity profile suggesting this use earlier and in combination in the therapeutic course of B-precursor acute lymphoblastic leukaemia patients. In this article, after a short overview of immunotherapeutic advances in B-precursor acute lymphoblastic leukaemia, the results of the main trials conducted with blinatumomab are discussed and put in perspective.

(BELG J HEMATOL 2017;8(3):107–12)

Vascular safety profile of new generation BCR-ABL tyrosine kinase inhibitors in the treatment of chronic myeloid leukaemia

SUMMARY

Tyrosine kinase inhibitors targeting BCR-ABL have been a real revolution in the treatment of chronic myeloid leukaemia, greatly improving surrogate outcomes and overall survival. However, new generation BCR-ABL tyrosine kinase inhibitors have recently been associated with occurrence of cardiovascular events. Indeed, during ponatinib clinical development, a high rate of patients with chronic myeloid leukaemia developed a vascular occlusive event. Retrospective analyses also demonstrated an increased incidence of similar events with nilotinib. Recently, a meta-analysis of randomised clinical trials confirmed this risk with nilotinib and ponatinib, but also identified dasatinib at higher risk of cardiovascular events than imatinib. Sub-analysis of this meta-analysis and retrospective studies indicated predominance of arterial events rather than venous. The number of patients treated with dasatinib and nilotinib has considerably increased since they have been approved in first-line indication for patients with chronic-phase chronic myeloid leukaemia. In this context, the evaluation of the benefit-risk profile of these treatments is important, and implementation of measures to minimise the onset of cardiovascular events are required. They should include the selection of patients treated with new generation tyrosine kinase inhibitors, the monitoring of cardiovascular events and risk factors during treatment, and if required, the treatment of cardiovascular comorbidities. The pathophysiology of these events is probably multifactorial. Numerous hypotheses have already been advanced and suggest a worsening of the metabolic syndrome, an increase of atherosclerosis development and an impact of new generation tyrosine kinase inhibitors on off-targets related to vascular function.

(BELG J HEMATOL 2017;8(2):45–52)

O.5 Sequential administration of 5-azacytidine (AZA) and donor lymphocyte infusion (DLI) for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in relapse after allogeneic stem cell transplantation (SCT): an interim analysis from the Belgian Hematology Society (BHS)

Highlights in acute myeloid leukemia (AML): what is going to change?

SUMMARY

The decision making process in AML integrates clinical features, an increasing amount of genetic information and minimal residual disease (MRD) data. Combining these data aims at answering the following questions:

• do I treat my patient with an intensive (= curative) or a non intensive (= non-curative) approach ?
• do I have therapeutic targets to improve the current treatment?
• is there an indication for a stem cell transplantation (SCT), maintenance therapy, etc.

Each new edition of ASH brings some new answers. This was again the case at the 2016 annual ASH meeting.

(BELG J HEMATOL 2017;8(1):29–33)

P1.11 Retrospective Chart Review of Hospitalisations and Costs Associated with the Treatment of Adults with Philadelphia-negative (-) B-precursor Relapsed or Refractory (R/R) Acute Lymphoblastic Leukemia (ALL) in Belgium

PP4.2 The clinical relevance of imatinib (Im) plasma trough concentration in patients with chronic myelocytic leukemia (CML) in chronic phase. A Belgian retrospective study

O.5 BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia: a systematic review and meta-analysis on the risk of cardiovascular events, major molecular response and overall survival