A Staged Approach to the Use of Bortezomib/Thalidomide/Dexamethasone (VTD) in Multiple Myeloma Patients with Suboptimal Initial Cytoreduction Led to a High Complete Remission Rate

Autologous hematopoietic stem cell transplantation (AHSCT) and bortezomib are the two most important advances in the treatment of multiple myeloma (MM) in the last decade. Autologous HSC harvest is preferably performed at complete remission (CR) or after maximal reduction of myeloma tumor load. Owing to the high cost of bortezomib, we devised a total therapy incorporating VAD (vincristine, adriamycin, dexamethasone), followed by VTD in those with inadequate cytoreduction (i.e. <75% reduction in paraprotein) to maximize eradication of myeloma cells in the marrow prior to HSC harvest. Those achieving >75% paraprotein reduction proceeded to AHSCT directly. Those with measurable disease after the first AHSCT proceeded to second AHSCT. Response was based on the EBMT criteria (Blade et al, 1998). There were 16 patients with a median age of 50 years (33–64). Majority had advanced stage disease by International staging system. After VAD, 6 patients had >75% response (>90% response, n=3; 75%–90% response, n=3) and hence proceeded to first AHSCT directly. The other 10 patients had VTD salvage therapy, which upgraded response in 9 cases. After VAD and VTD treatments, there were 2, 6,7 and 1 patients achieving CR, >90% response, 75%–90% response and no response respectively. Thirteen patients proceeded to the first AHSCT, which rendered upgrading of response in 9 patients (69%) with CR/near CR in 7 cases (54%) and >90% response in 4 cases (31%). The latter 4 patients proceeded to second AHSCT, resulting in CR/near CR in 9 cases (70%) and >90% in 2 cases (15%). Of the 11 patients with >90% response after first and/or second AHSCT, 5 patients had maintained response with continual CR in 4 cases, whereas 6 patients relapsed (with asymptomatic disease in 4 cases and fatality in 2 cases). Therefore, this strategy of employing bortezomib only in those with insufficient cytoreduction achieved a high CR/near CR rate comparable to that with upfront bortezomib use. However, the frequent relapse implied that the quality of CR is equally important. Moreover, the aggressive fatal relapse in CR patients demonstrated a biologically aggressive subgroup in which CR might be inadequate.