New drugs in the therapy of multiple myeloma

Abstract

The introduction of the BCR-ABL kinase inhibitor, imatinib mesylate (Gleevec®, Novartis) Artigo / Article REVISTA BRASILEIRA DE HEMATOLOGIA E H E M O T E R A P I A REVISTA BRASILEIRA DE HEMATOLOGIA E H E M O T E R A P I A Department of Clinical and Biological Sciences, University of Turin -Italy Ospedale San Luigi Orbassano -Medicina Interna -10043 Correspondence: Daniela Cilloni Department of Clinical and Biological Sciences, University of Turin -Italy Ospedale San Luigi Orbassano -Medicina Interna -10043 E-mail: daniela.cilloni@unito.itThe first BCR-ABL inhibitor to come into the clinical practice, imatinib mesylate, is now the first-choice of treatment for all newly diagnosed CML patients. This drug was tested in phase I and II clinical trials and soon moved to a phase III randomised trial (International Randomised Study of Interferon versus ST1571 [IRIS]) in which the drug was compared with interferon alfa plus cytosine arabinoside (IFNα plus ARA-C). 1The treatment provides an impressive rate of complete haematological responses (CHR) and complete cytogenetic remissions (CCgR), assessed at 95% and 94%, respectively for imatinib, compared with 55% and 8.5% for IFNα -ARA-C. Progression free survival at 18 months was 96.7% for imatinib compared with 91.5% for IFNα ARA-C . The data coming from the IRIS trial have been recently updated 2 and show that the cumulative incidences of CHR and CCgR at 5 years are 98% and 87%, respectively, for imatinib. For those patients achieving a CCgR at 18 months or for patients obtaining a major molecular response (MMR) (three-log reduction in leukemic cells), the 5-year progressionfree survival is 97% and 99%, respectively. Despite the impressive percentage of responding patients, some CML cases, particularly in the more advanced phases of the disease, show primary resistance or relapse after an initial response.

Multiple myeloma: the disease and its treatment

“…Consequently, single-agent dexamethasone is no longer recommended as initial therapy. 62 Thalidomide combined with dexamethasone is an effective pre-transplantation induction regimen. 63 The most frequent adverse effects seen with thalidomide based regimens were somnolence, constipation, neuropathy and fatigue.…”

“…Aspirin can be used instead in patients receiving only low doses of dexamethasone (40 mg, 4 days a month or lower) or prednisone in combination with thalidomide, provided no concomitant erythropoietic agents are used. 62 Another regimen with high anti-myeloma activity is the association of bortezomib (Velcade) and dexamethasone. 77,78 Bortezomib is a potent, reversible, and selective inhibitor of the 26S proteasome targets the myeloma cell and the bone marrow microenvironment and acts by inhibiting the binding of myeloma cells to stromal cells and decrease bone marrow triggered angiogenesis.…”