Consolidation therapy with bortezomib/lenalidomide/dexamethasone (VRD) followed by maintenance with lenalidomide until progression or toxicity showed promising results over maintenance alone for patients with transplant-eligible multiple myeloma (NDMM) up to 65 years old, according to a final analysis of the EMN02 trial.
This study prospectively addressed the role of upfront consolidation in patients newly diagnosed with NDMM. Between February 2011 and April 2014, 1510 patients ≤65 years with symptomatic multiple myeloma were enrolled, of whom 1499 were eligible. Of these, 1211 were first randomized (R1) and stratified by International Staging System (ISS) stage, to 4 cycles of bortezomib/melphalan/prednisone (VMP; n = 505) or high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT; n = 706; 1 or 2 ASCT) as intensification therapy after induction with VCD.
The second randomization (R2) to consolidation therapy (n = 444) with 2 cycles of VRD versus no consolidation (n = 459) was performed after intensification. This was followed by lenalidomide maintenance at 10 mg continuously. Patient characteristics at baseline were similar between the 2 arms. FISH was used at diagnosis to assess cytogenetics, and the FISH status was found to be similar between the 2 arms.
“As for the second randomization, we saw no difference in consolidation between patients receiving 1 or 2 transplants,” explained Pieter Sonneveld, MD, PhD, at the Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands.
PFS from R2 adjusted for R1 was prolonged in patients randomized to VRD (HR, 0.78; 95% CI, 0.61-1.00;P= .045). The benefit of VRD on PFS was retained across predefined subgroups with revised ISS stage III (HR, 0.67;P= .26). This benefit was also retained in patients randomized in R1 to VMP (HR, 0.76;P= .19) and to HDM (HR, 0.79;P= .13).
“PFS from second randomization with adjustment for the first randomization was prolonged in patients randomized to consolidation,” stated Sonneveld.
The benefit of consolidation, however, was observed in patients with low-risk cytogenetics (HR, 0.68;P= .03), but not in patients with high-risk cytogenetics (del[17p], t[4;14] and/or t[14;16]; HR, 1.03;P= .91).
“The benefit of consolidation was primarily observed in patients with low-risk cytogenetics but not in patients with high-risk cytogenetics, deletion 17p, t(4;14), and t(14;16),” Sonneveld explained.
PFS for R2 was 62% in all patients. In other words, PFS was 60% in patients without consolidation and 65% in patients with consolidation. There were 258 events for PFS after R2 reported.
At 3 years, OS was 86% in both arms. Median follow-up from R2 was 25 months (maximum 53).
At the time of R2, 23% experienced a CR or higher, 67% at least a very good partial response, and 93% experienced a partial response or higher.
Toxicity from VRD was limited with 5% Common Terminology Criteria for Adverse Events (CTCAE) grade 4, most of which were hematological. Cytopenia and thrombocytopenia were observed with no other unexpected toxicities.
A central MRD analysis was organized across 4 European countries. The samples were assessed for quality several times. From the MRD analyses, they concluded that main analysis is possible. These results are expected to be present at the 2017 ASCO Annual Meeting and/or the 2017 EHA Annual Congress.
The EMN011 trial established a first relapse protocol after EMN01. This protocol uses pomalidomide (Pomalyst), carfilzomib (Kyprolis), and dexamethasone. This trial is ongoing, and data will be presented in the future.
“In conclusion, this is the first analysis of the EMN02 trial and also the first trial that prospectively addressed consolidation treatment versus no consolidation treatment in the transplant setting, and we conclude that in this analysis we see an improvement of CR rates,” concluded Sonneveld.
Unrestricted grants from Celgene and Janssen supported this trial.
Sonneveld P, Beksac M, van der Holt B, et al. Consolidation Followed By Maintenance Therapy Versus Maintenance Alone in Newly Diagnosed, Transplant Eligible Patients with Multiple Myeloma (MM): A Randomized Phase 3 Study of the European Myeloma Network (EMN02/HO95 MM Trial). Presented at: the 58th Annual Meeting of the American Society of Hematology; Dec 3-6, 2016; San Diego, California. Abstract 242.