Bortezomib/lenalidomide/dexamethasone (RVd) has not been compared to other triplet induction regimens (cyclophosphamide, bortezomib, dexamethasone [CyBorD or VCD] and bortezomib, thalidomide, dexamethasone [VTD]) in a phase III randomised study. However, on the basis of cross-trial comparisons of response rates and toxicity, the expert reference panel supports the use of RVd as induction treatment for transplant eligible patients with multiple myeloma (MM). The dosing schedule in this eviQ protocol is based on the phase III study, IFM 2009.r
In the IFM 2009 study, patients received three cycles of RVd induction and were then randomised to either (a) autologous stem cell transplant (ASCT) followed by two cycles of RVd consolidation or (b) five further cycles of RVd. The superiority of an upfront ASCT approach was confirmed with patients randomised to the transplant arm having a significantly prolonged progression-free survival (PFS) of 50 months compared with 36 months.r
Efficacy
The rate of complete response was 48% in the RVd-alone group versus 59% in the ASCT group (P = 0.03). The rate of very good partial response or better was 45% in the RVd-alone group versus 47% in the ASCT group after induction, 69% versus 78% after the consolidation phase (P = 0.03) and 76% versus 85% after the maintenance phase (P = 0.009).r
Updated data presented at ASH 2020, with a median follow-up of 89.8 months, demonstrated a PFS of 47.3 months in the transplantation arm versus 35 months in the RVd-alone arm (p < 0.001). There was no difference in overall survival (OS) between the two arms, with an 8 year OS in the RVd-alone arm of 60.2% and in the ASCT arm of 62.2% (P = 0.815).r
Toxicity
The most common Grade 3 and 4 toxicities are documented in the table below. The most clinically significant toxicities for this treatment are haematological toxicities and peripheral neuropathy. Grade 3/4 haematological toxicity was seen in 63% in the RVd-alone group and 93.9% in the transplantation group. Infections were seen in 8.9% of the RVd-alone group and 20.3% in the transplantation group. Peripheral neuropathy was seen in 13.7% in the RVd-alone group and 12.9% in the transplantation group, grade 2 painful neuropathy was seen in 0.9% and 8% of patients respectively. Treatment discontinuation occurred in 9% of patients in the RVd-alone group with two treatment-related deaths and in 11% in the transplantation group with six treatment-related deaths.r
Table 3 - Grade 3 and 4 Adverse Eventsr
© NEJM 2017