PHARMACOTHERAPY

Proteasome inhibitors in multiple myeloma and other haematological malignancies

Summary

The proteasome is an important anticancer target. Bortezomib, as a first-in-class proteasome inhibitor has become a valuable drug in the therapeutic armamentarium against multiple myeloma. This drug-review summarises the current indications for the use of bortezomib in myeloma. In addition, its emerging role as a consolidating / maintenance agent after autologous stem cell transplantation and its use in patients with bad cytogenetical markers or renal impairment is addressed. We also include the available data on the subcutaneous route of administration as an alternative to mitigate peripheral neuropathy. The promising evidence of proteasome inhibitors in other haematological malignancies (low grade lymphomas, mantle cell lymphoma, Waldenström’s disease and systemic amyloidosis) is also summarised.

(BELG J HEMATOL 2012;3:95–104)

Dasatinib (Sprycel®) use in daily clinical practice: a Belgian observational retrospective study in patients with chronic myeloid leukaemia and Philadelphia positive acute lymphatic leukaemia who are resistant or intolerant to prior therapies including imatinib

Summary

This study aimed to collect information on daily clinical use of dasatinib (Sprycel®) in Belgium, when used for treating patients with chronic myeloid leukaemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) with resistance or intolerance to prior therapies including imatinib.

We used an observational retrospective approach to collect data from 84 patients (72 CML and 12 Ph+ ALL) from 23 Belgian centres who received dasatinib in the period between October 1, 2007 and October 31, 2009.

The majority of patients had been diagnosed with chronic phase CML (69%). All patients had received prior treatment with imatinib before initiation of dasatinib. Main reasons for switching to dasatinib were development of resistance (65%) or intolerance (31%). In 89% of chronic and accelerated phase CML patients, dasatinib therapy induced complete haematological response (CHR). Major cytogenetic response (MCyR) was observed in 63% and 67% of chronic and accelerated phase patients, respectively.

This study population is representative for patients receiving dasatinib treatment in Belgium. Dasatinib was well tolerated and patient outcome confirmed dasatinib use has significant clinical value in the treatment of CML and Ph+ ALL patients with resistance or intolerance to prior imatinib therapy.

(BELG J HEMATOL 2012;3:51–58)

Clofarabine in clinical haematology

Summary

Clofarabine is a second-generation nucleoside analogue which has been rationally developed with the aim to combine the therapeutic qualities and avoid the toxic limitations of fludarabine and cladribine. Clofarabine has been reimbursed in Belgium for the treatment of paediatric patients up to the age of 21 years with relapsed or refractory Acute Lymphatic Leukaemia (ALL) after two or three preceding regimens respectively. Clinical efficacy has also been demonstrated in newly diagnosed and advanced Acute Myoblastic Leukaemia (AML). The drug is currently being investigated in several randomised trials in AML and ALL and as part of the conditioning regimen prior to stem cell transplantation. This article focuses on the pharmacology, toxicity and clinical efficacy of clofarabine.

(BELG J HEMATOL 2012;3:17–22)