Bortezomib Regimens Show Similar Efficacy in Transplant-Eligible NDMM

“[Randomized clinical trials] comparing the safety and efficacy of VTD and VRD induction are needed to identify the most appropriate regimen for patients with transplant-eligible NDMM," according to the study authors.

Induction therapy with bortezomib (Velcade) plus thalidomide and dexamethasone (VTD) demonstrated comparable efficacy outcomes vs bortezomib plus lenalidomide (Revlimid) and dexamethasone (VRD) in the treatment of patients with transplant-eligible newly diagnosed multiple myeloma (NDMM), according to findings from a systematic review published in Hematology.¹

Based on random-effects model analysis, the average objective response rate (ORR) was 93% (95% CI, 87%-97%) in patients receiving VTD (n = 679), which showed significant heterogeneity across studies (I² = 77%; P <.01). The average very good partial response (VGPR) rate was 61% (95% CI, 55%-67%) in this group, with significant heterogeneity reported across studies (I² = 53%; P = .007).

Among patients who received VRD (n = 1894), the average ORR was 86% (95% CI, 81%-91%); the heterogeneity across studies that assessed VRD was lower compared with that reported in VTD-based studies (I² = 87%; P <.01). The average VGPR or better rate in this group was 60% (95% CI, 49%-71%), which showed substantial heterogeneity (I² = 92%; P <.01).

Overall, data showed a significant difference in ORR (P <.01) and at least VGPR (P = .04) values between patients who received VTD and those who were treated with VRD. Investigators noted a potentially higher ORR and likelihood of achieving a VGPR or better with VTD than VRD.

“Although VTD induction showed statistically better ORR and VGPR values compared to VRD induction, the numerical difference was not substantial. These results suggest that both VTD and VRD may represent appropriate induction regimens for [patients with] NDMM,” Yin-Che Wang, from the Division of Hematology/Medical Oncology, Department of Medicine at Taichung Veterans General Hospital, wrote with study coauthors.¹

“Notably, the patients who received VTD induction had a significantly higher chance of undergoing autologous hematopoietic stem cell transplantation [auto-HSCT] than those who received VRD induction. Since auto-HSCT still provides a progression-free survival [PFS] benefit to patients with NDMM in the era of novel agents, VTD may represent an ideal induction backbone in the context of transplant-eligible NDMM,” the authors added.^1,2

Investigators of this systematic review and meta-analysis evaluated 15 studies assessing induction therapy for patients with transplant-eligible NDMM, which included 6 evaluating VTD and 9 investigating VRD.

The study’s primary end point was ORR following induction therapy; due to the nature of a meta-analysis, the investigators noted that the number of induction therapy cycles was variable across the assessed trials. The secondary end point was the rate of patients who underwent auto-HSCT. Investigators also evaluated grade 3 or 4 hematological, infection-related, and thrombotic adverse effects (AEs).

Phase 2 or 3 studies that prospectively enrolled patients with NDMM, transparently reported treatment strategies, and clearly defined assessments of therapeutic outcomes of interest were included in the meta-analysis. Studies that assessed patients with transplant-ineligible NDMM were not included in the analysis.

Treatment protocols in the VTD studies demonstrated relative consistency, and the median ages ranged from 56 to 73 years. The number of treatment cycles in these studies ranged from 2 to 6. Greater variability in treatment dosing and schedules was observed in the VRD studies; the median ages ranged from 57 to 63 years. Additionally, the number of VRD cycles ranged from 3 to 12.

Across 6 studies including 1222 patients, the average auto-HSCT rate in patients who received VTD was 93% (95% CI, 85%-98%), which showed significant heterogeneity (I² = 93%; P <.01). Regarding 5 studies that assessed the use of VRD in 2153 patients, the average auto-HSCT rate was 67% (95% CI, 51%-82%), and the heterogeneity was high (I²= 99%; P <.01). Investigators highlighted a potentially higher effect with VTD vs VRD on the rate of auto-HSCT (P <.01).

The average rate of grade 3/4 hematological AEs was 31% (95% CI, 11%-56%) with VTD, which showed substantial heterogeneity (I² = 95.0%; P <.01). The respective rate was 33% (95% CI, 18%-49%) with VRD, which demonstrated high heterogeneity (I² = 98.7%; P <.01). Data indicated that the rate of grade 3/4 hematological AEs was not significantly lower with VTD vs VRD (P = .13).

The average rate of infection-related AEs was 9% (95% CI, 3%-18%) with VTD, with substantial heterogeneity reported across studies (I² = 90.1%; P <.01). In the VRD population, the average rate was 14% (95% CI, 9%-19%); studies showed substantial heterogeneity (I² = 93.1%; P <.01). Data showed a significantly reduced risk of grade 3/4 infections with VTD (P <.01).

On average, thrombotic AEs were reported in 4% (95% CI, 1%-8%) of patients who received VTD, with substantial heterogeneity between studies (I² = 73.1%; P <.01). In the VRD group, the average thrombotic AE rate was 3% (95% CI, 1%-4%), and the heterogeneity between studies was substantial (I² = 70.9%; P <.01). Investigators noted a significantly lower risk of grade 3/4 thrombotic AEs in the patients who received VRD (P <.01).

“[Randomized clinical trials] comparing the safety and efficacy of VTD and VRD induction are needed to identify the most appropriate regimen for patients with transplant-eligible NDMM,” the study authors concluded.¹

References

1. Wang Y-C, Lin C-H, Su Y-C, Jerry Teng C-L. Bortezomib, thalidomide, and dexamethasone versus bortezomib, lenalidomide, and dexamethasone in transplant-eligible newly diagnosed multiple myeloma: a systemic review and meta-analysis. Hematology. 2025;30(1):2462249. doi:10.1080/16078454.2025.2462249
2. Richardson PG, Jacobus SJ, Weller EA, et al. Triplet therapy, transplantation, and maintenance until progression in myeloma. N Engl J Med. 2022;387(2):132-147. doi:10.1056/NEJMoa2204925