Extended maintenance with VRD in NDMM: A 15-year follow-up

High-risk multiple myeloma (MM) presents with typically more progressive disease and poorer outcomes than those with standard or low-risk disease. During the maintenance period of treatment, the addition of a proteasome inhibitor to standard-of-care treatment is suggested. One of the maintenance combinations being investigated for these high-risk patients is the proteasome inhibitor bortezomib, with lenalidomide and dexamethasone (VRD).

Here, we summarize a publication by Al Hadidi et al.¹ in Blood Advances on the 15-year follow-up results of extended maintenance with VRD in newly diagnosed MM from the total therapy (TT) IIIB cohort of the UARK 2006-66 study (NCT00572169).

Study design and patient population¹

• TT IIIB was an extension of the UARK 2003-33 (NCT00081939) TT III study, comparing the impact of three years of maintenance with VRD with one year of bortezomib, thalidomide, dexamethasone followed by two years of thalidomide and dexamethasone maintenance in TT IIIA.
• A 15-year follow-up analysis assessed the long-term outcomes in patients (21% with gene expression profile (GEP)-defined high-risk MM) who received extended VRD maintenance.

Key findings¹

• After a median follow-up of 15.4 years, median progression-free survival (PFS) was 5.6 years and overall survival (OS) was 9.1 years. PFS and OS rates throughout the follow-up period are shown in Figure 1.
• Overall, the following GEP-defined low-risk vs high-risk patient outcomes were recorded, respectively:
  • median PFS; 7.8 years and 2.2 years; and
  • median OS; 11.2 years and 2.8 years.
• TT IIIB did not result in improvement of OS compared with TT IIIA at a hazard ratio of 1.2 (95% confidence interval [CI], 0.9–1.5; P = 0.166)
• PFS was poorer in TT IIIB than in TTIIIA at a hazard ratio of 1.3 (95% CI, 1.0–1.6; P = 0.048)
• Patients treated in TT IIIB vs TT IIIA had a higher incidence of certain adverse factors, including low albumin levels (45% vs 26%, respectively) and high β2 microglobulin levels (57% vs 45%, respectively.

OS, overall survival; PFS, progression-free survival.
*Data from Al Hadidi, et al.¹

Key learnings
An extended maintenance period of three years vs one year with bortezomib therapy did not improve outcomes such as OS and PFS. Patients with GEP-defined high-risk MM experienced poorer outcomes than those with low-risk MM. These data highlight an unmet need in effective maintenance strategies for patients with high-risk disease.