Abstract
BackgroundBortezomib, an NFkB inhibitor, is an active agent for the treatment of myeloma (MM). We have reported a promising complete remission (CR) rate for newly diagnosed myeloma patients treated by a staged approach, in which chemosensitive patients underwent autologous haematopoietic stem cell transplantation (auto-HSCT) while less chemosensitive patients received salvage therapy with bortezomib/thalidomide/dexamethasone prior to auto-HSCT.MethodsHerein, with an additional 13 months of follow-up, we reported the updated survivals, and examined potential prognostic factors impacting event-free (EFS) and overall survival (OS).ResultsWith a median follow-up of 30 months, the projected OS was 73% and EFS was 50.2%. Age, gender, clinical stage and DAPK methylation could not account for the differential chemosensitivity. Advanced ISS stage and DAPK methylation adversely impacted OS whereas oligoclonal reconstitution predicted superior EFS.ConclusionsOur staged approach illustrated an economical use of expensive targeted agents while preserving a good CR rate and OS. The comparable survivals of chemosensitive and less chemosensitive patients suggested the staged approach might have abolished the adverse prognostic impact of suboptimal chemosensitivity. Finally, the adverse impact of DAPK methylation and favorable impact of oligoclonal reconstitution in myeloma warrants further study.
Highlights
Bortezomib, an NFkB inhibitor, is an active agent for the treatment of myeloma (MM)
Correspondence: jcschim@hku.hk Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong patients were risk-stratified according to their initial chemosensitivity, wherein VAD-chemosensitive patients underwent autologous hematopoietic stem cell transplantation while less VAD-chemosensitive patients received salvage therapy of bortezomib/thalidomide/dexamethasone (VTD) before auto-HSCT.5 (Figure 1) We have reported frequent occurrence of oligoclonal reconstitution, frequent central nervous system myeloma and absence of thalidomide-related deepvein thrombosis despite no prophylaxis with either aspirin, low molecular weight heparin or warfarin [5]
Comparing the VAD-chemosensitive with the less chemosensitive subgroups, there was no significant difference in the median age and distribution of gender, paraprotein subtypes and International Stage. (Table 1) Of the 22 patients with methylation study data, four (18.2%) carried Death-associated Protein Kinase (DAPK) methylation
Summary
We have reported a promising complete remission (CR) rate for newly diagnosed myeloma patients treated by a staged approach, in which chemosensitive patients underwent autologous haematopoietic stem cell transplantation (autoHSCT) while less chemosensitive patients received salvage therapy with bortezomib/thalidomide/dexamethasone prior to auto-HSCT. After the demonstration of its efficacy as salvage therapy in chemo-resistant or refractory myeloma patients with a CR rate of 9% [1,2]. A high CR rate has been demonstrated when bortezomib was used in induction therapy in newly diagnosed myeloma patients. A CR rate of 43% and 30% was observed when bortezomib-based induction therapy was applied in both transplant-eligible and transplant-ineligible myeloma patients [3,4]. In Hong Kong, we have adopted a staged approach, in which newly diagnosed, transplant-eligible myeloma Low-Risk Chemosensitive VAD (n=25) t75% (n=11) RESPONSE High-Risk
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call