Benefits of additional cycles of bortezomib/thalidomide/dexamethasone (VTD) induction therapy compared to four cycles of VTD for newly diagnosed multiple myeloma

Abstract

Bortezomib/thalidomide/dexamethasone (VTD) induction therapy followed by autologous stem cell transplantation (ASCT) is one of the standard therapies for newly diagnosed multiple myeloma (NDMM). However, the appropriate depth of response to induction therapy and timing of upfront ASCT are still debated. We investigated if two additional cycles of VTD (VTD6) improved the responses and progression-free survival (PFS) compared with four cycles of VTD (VTD4). We retrospectively reviewed outcomes of 190 NDMM patients treated with at least four cycles of VTD followed by ASCT between September 2014 and August 2017 [VTD4, n = 129 (67.9%); VTD6, n = 61 (32.1%)]. The VTD6 group had a higher pre-ASCT complete response (CR) rate than the VTD4 group (31.1% versus 10.1%, P < 0.001), but, the pre- and post-ASCT ≥ very good partial response (VGPR), and 2-year PFS were similar. Multivariate analysis revealed age, β₂-microglobulin, and pre-ASCT CR as important factors for PFS. Two additional cycles of VTD prolonged PFS in patients with PR only after VTD4 [Hazard ratio (HR) = 0.29, P = 0.016] or those with Revised International Staging System stage I/II (HR = 0.36, P = 0.039). In conclusion, two additional VTD cycles may be helpful for patients with PR only after VTD4 but high risk MM needs the other treatment options.

Fig. 1

Survival rates according to the two additional cycles of VTD. a Progression-free survival (PFS): The 2-year PFS rate was 64.4 ± 5.0% and 68.9 ± 8.3% for the VTD4 and VTD6 groups, respectively (P = 0.189). b Overall survival (OS): The 2-year OS rate was 88.6 ± 3.2% and 95.4 ± 3.4 % for the VTD4 and VTD6 groups, respectively (P = 0.291)

Fig. 2

Survival rates in the VTD4 and VTD6 groups according to the response after four cycles of VTD. Patients with partial response only after four cycles of VTD showed superior (a) 2-year Progression-free survival (PFS) in the VTD6 groups (74.4 vs 52.2%, P = 0.022). b The 2-year overall survival (OS) rate in these patients was not different. Patients who already achieved CR/VGPR after four cycles of VTD showed similar survival rates. c The 2-year PFS was 67.4 ± 5.6% and 75.2 ± 10.0% in VTD4 and VTD6 groups, respectively (P = 0.615). d The 2-year OS was 92.0 ± 3.0% and 96.4 ± 3.5% in VTD4 and VTD6 groups, respectively (P = 0.620)

Fig. 3

Survival benefit from two additional cycles of VTD by Revised International Staging System (R-ISS). Patients with R-ISS stage I/II showed superior (a) The 2-year Progression-free survival (PFS) in the VTD6 group (67.8 ± 6.3% vs 90.2 ± 6.9%, P = 0.045). b The 2-year overall survival (OS) rate in these patients was not different. Patients with R-ISS stage III showed similar 2-year PFS (c) and the 2-year OS (d)