For transplant-eligible patients with multiple myeloma (MM), consolidation with high-dose melphalan (HDM) followed by autologous stem-cell transplantation (ASCT) remains a preferred option. The HOVON-65/GMMG-HD4 trial had previously demonstrated that incorporation of bortezomib to induction and maintenance regimens followed by HDM and ASCT resulted in a significant improvement in progression-free survival (PFS) and overall survival (OS) in transplant-eligible patients with newly diagnosed MM compared with standard regimens.1
To evaluate the long-term impact of these 2 therapeutic options, 827 eligible patients were randomized to receive standard induction therapy with vincristine/doxorubicin/dexamethasone (VAD) or the bortezomib-containing regimen of bortezomib/doxorubicin/dexamethasone (PAD). Following HDM/ASCT, maintenance therapy consisted of a daily thalidomide (T) regimen (50 mg) in the VAD arm, or twice-weekly bortezomib (B) treatment (1.3 mg/m2) in the PAD arm for 2 years. After a median follow-up of 91.4 months, response rates were significantly higher in the bortezomib-containing arm (PAD/HDM/B) compared with the standard arm (VAD/HDM/T). Likewise, PFS was significantly higher in the bortezomib-containing arm, with a median PFS of 34 months versus 28 months in the standard arm (P = .001). Furthermore, median OS was 90 months in the bortezomib arm versus 83 months in the standard arm. Although administration of single versus double HDM/ASCT did not impact PFS at 60 months in the bortezomib-containing arm, OS at 60 months was improved with double HDM/ASCT (71% vs 60%; P = .04). The findings of a subgroup analysis in 395 patients who underwent double HDM/ASCT based on the presence or absence of adverse chromosomal abnormalities showed that bortezomib treatment plus double HDM/ASCT in the subset of patients with del(17p) significantly improved PFS and OS, while it did not benefit patients with t(4;14) or gain(1q) abnormalities. Similar improvements in PFS at 60 months (32% vs 5%; P = .001) and OS at 60 months (66% vs 21%; P <.001) were achieved by high-risk patients presenting with elevated creatinine >2 mg/dL.
The long-term results of the HOVON-65/GMMG-HD4 trial showed that bortezomib-based induction and maintenance leads to significant and durable improvements in survival. This survival advantage extends to patients with del(17p) and elevated creatinine, which is a marker of renal impairment.
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