Adding bortezomib to high-dose melphalan (HDM) conditioning does not improve post-transplant outcomes in patients with newly diagnosed multiple myeloma, according to a phase 3 study published in Blood.
Bortezomib did not improve complete response (CR) rates, progression-free survival, or overall survival, when compared with HDM alone.
This phase 3 trial (ClinicalTrials.gov Identifier: NCT02197221) enrolled 300 patients with newly diagnosed multiple myeloma. The patients were randomly assigned to receive bortezomib plus HDM (n=154) or HDM alone (n=146) before autologous stem cell transplant.
As frontline treatment, patients had received bortezomib, thalidomide, and dexamethasone (89.0% in the bortezomib arm and 85.6% in the HDM arm) or bortezomib, cyclophosphamide, and dexamethasone (10.0% and 12.3%, respectively). More than half of patients (58.4% and 56.8%, respectively) had a very good partial response or better after induction.
The primary endpoint was CR or stringent CR at 60 days after transplant. There was no significant difference in this endpoint between the bortezomib arm and the HDM-alone arm — 22.1% and 20.5%, respectively (P =.844).
Likewise, there was no significant difference in the rate of undetectable minimal residual disease at 60 days between the bortezomib arm and the HDM-alone arm — 41.3% and 39.4%, respectively (P =.864).
The median follow-up was 34.3 months in the bortezomib arm and 35.8 months in the HDM arm.
The median progression-free survival was 34.0 months in the bortezomib arm and 29.6 months in the HDM arm (hazard ratio [HR], 0.82; 95% CI, 0.61-1.13; P =.244). The estimated 3-year overall survival rate was 89.5% in both arms (HR, 1.28; 95% CI, 0.62-2.64; P =.374).
Serious adverse events (AEs) were observed in 18.7% of patients in the bortezomib arm and 13.1% in the HDM arm. Treatment-emergent AEs were observed in nearly all patients — 96.0% in the bortezomib arm and 93.8% in the HDM-alone arm.
The rate of grade 3/4 treatment-emergent AEs was 54.0% in the bortezomib arm and 58.6% in the HDM arm. Hematologic and gastrointestinal AEs were the most common.
The rate of treatment-emergent peripheral neuropathy was 46.0% in the bortezomib arm and 29.7% in the HDM-alone arm.
Based on these results, the researchers concluded that HDM “remains the standard of care conditioning for transplant in multiple myeloma.”
Disclosures: This research was supported by Janssen-Cilag and the French government. The study authors declared no competing financial interests for this trial, but some have relationships with Janssen-Cilag. Please see the original reference for a full list of disclosures.
Roussel M, Lauwers-Cances V, Macro M, et al. Bortezomib and high-dose melphalan conditioning regimen in frontline multiple myeloma, an IFM randomized phase 3 study. Blood. Published online March 16, 2022. doi:10.1182/blood.2021014635