PHARMACOTHERAPY

Therapeutic vaccination against acute myeloid leukaemia using dendritic cells

Summary

The prognosis of patients with acute myeloid leukaemia (AML) remains dismal, with a five year overall survival rate of only 5.2% for the continuously growing subgroup of AML patients older than 65 years. These patients are generally not considered eligible for intensive chemotherapy and/or allogeneic haematopoietic stem cell transplantation, emphasising the need for novel, less toxic treatment alternatives for the older-age category of AML patients. It is within this context that immunotherapy has gained attention in recent years. In this review, we focus on the use of dendritic cell (DC) vaccines for immunotherapy of AML. DCs are the central orchestrators of the immune system bridging innate and adaptive immunity and are critical to the induction of anti-leukaemia immunity. Here, we discuss the rationale and basic principles of DC-based therapy for AML and review the clinical experience that has been obtained so far with this form of immunotherapy in patients with AML.

(BELG J HEMATOL 2013;4(2):58–65)

Immunomodulatory drugs: new developments

Summary

The immunomodulatory drugs (IMiDs) are a class of orally available compounds which are licensed for the treatment of multiple myeloma (thalidomide, lenalidomide) and transfusion-dependent low- and intermediate-risk myelodysplasia (MDS) with deletion of long arm of chromosome 5 (lenalidomide). Pomalidomide, a novel second generation IMiD, is entering clinical trials and seems to further broaden the therapeutic spectrum of these already pleiotropic drugs. Here we summarise new insights into the mechanism of action of IMiDs as well as new developments related to their clinical use, as maintenance therapy in multiple myeloma (MM), in the treatment of myeloproliferative neoplasm- associated myelofibrosis, other types of MDS, chronic lymphocytic leukaemia (CLL) and sickle cell disease (SCD).

(BELG J HEMATOL 2013;1:21–28)

Brentuximab vedotin: an innovative treatment for patients with Hodgkin and systemic anaplastic large cell lymphoma

Summary

Brentuximab vedotin is an anticancer antibody-drug conjugate: it comprises an anti-CD30 monoclonal antibody conjugated to MMAE ( monomethyl auristatin E), a synthetic tubulin polymerisation inhibitor. The drug is given intravenously every three weeks. It has been used in treatment of relapsed Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). Excellent results were obtained in these indications. Trials are underway in combination with chemotherapy for first line treatment.

(BELG J HEMATOL 2012;4:145–149)

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)