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A staged approach with vincristine, adriamycin, and dexamethasone followed by bortezomib, thalidomide, and dexamethasone before autologous hematopoietic stem cell transplantation in the treatment of newly diagnosed multiple myeloma
Annals of Hematology, 05/18/2010
Exclusive author commentary
Clinical Article
Chim CS et al. – In this study, the efficacy of a total therapy with a staged approach where newly diagnosed MM patients received vincristine/adriamycin/dexamethsone (VAD) was evaluated. This approach reduced the use of bortezomib without compromising the ultimate CR rate and is of financial significance for less affluent communities.
Methods- VAD-sensitive patients (≥ 75% paraprotein reduction) received autologous hematopoietic stem cell transplantation (auto-HSCT), whereas less VAD-sensitive patients (< 75% paraprotein reduction) received bortezomib/thalidomide/dexamethasone (VTD) for further cytoreduction prior to auto-HSCT
- On an intention-to-treat analysis, a progressive increase of CR rates was observed, with cumulative CR rates of 48% after HSCT
- 7 patients progressed leading to 3 fatalities, of which 2 had CNS disease
- 3-year OS and EFS were 75.1% and 48.3%
- 6 patients developed oligoclonal reconstitution with new paraproteins
- In the absence of anticoagulant prophylaxis, no patients developed deep vein thrombosis
- Staged application of VAD+/–VTD/auto-HSCT resulted in an appreciable response rate and promising survivals
chim et al (05/19/2010) comments:
This is a study to explore a risk-stratified approach in myeloma, in which patients were stratified by their initial chemosensitivity to VAD. Chemo-sensitive patients (i.e achieving >75% reduction in paraprotein) received auto-hematopoietic stem cell transplantation 9HSCT0, while less chemo-sensitive patients received salvage bortexomib-based therapy prior to auto-HSCT. This resulted in a CR rate and survival comparable to those studies employing bortezomib-based chemotherapy regimens upfront. However, in this staged approach, only 56% patients had bortezomib. Therefore, it would be an important approach in less affuent countries, by which optimal use of bortezomib would result in significant reduction in cost while preserving efficacy. Other important findings included the frequent CNS myeloma, frequent clonal evolutions and the absence of deep vein thrombosis even without prophylaxis.
