The 23rd Congress of the European Hematology Association (EHA) took place in Stockholm from 14–17 June 2018 and on Friday 15 June an oral session took place in which Pieter Sonneveld from the Erasmus MC Cancer Center, University of Rotterdam, the Netherlands, presented data from the second interim analysis of the phase III EMN02/HOVON 95 MM study, on behalf of all the EMN trial participants. This study is ongoing and compares bortezomib, melphalan, and prednisone (VMP) with bortezomib, lenalidomide, and dexamethasone (VRD), as consolidation regimens, along with lenalidomide maintenance, in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM).
The overall aims of the trial were to determine the efficacy of lenalidomide consolidation therapy following intensification therapy with either VMP or high-dose therapy (HDM), followed by consolidation with VRD. Patients were stratified according to the center and ISS disease stage, and randomized to receive either 4 cycles of VMP or HDM and autologous stem cell transplant (ASCT) in the first randomization (R1). Randomization was 1:1 in centers with a fixed single ASCT policy, and randomization to VMP, HDM-1, or HDM-2 was 1:1:1 in centers with a double ASCT policy. Following intensification, a second randomization (R2) to consolidation therapy with VRD was compared to no consolidation, followed by lenalidomide maintenance in both arms, until progression or toxicity. This talk focusses on data from R2.
- Patients (pts) aged ≤ 65 years with symptomatic MM (N = 1,510) were recruited between 14 February 2011 and 18 January 2018; pts = 1,211 randomized in R1: VMP (arm A) = 505 pts, HDM (1 or 2 ASCT) (arm B) = 706 pts
- For R2 (N = 916 pts eligible): no consolidation (arm A) = 437 pts and VRD consolidation (arm B) = 455 pts (24 pts were not eligible across both arms)
Data presented here focusses on R2 (no consolidation vs VRD consolidation):
- Pt characteristics between the two arms were well-matched
- Median follow up at R2 = 42 months (IQR 32–49, maximum 71)
- Best response before R2 (%): sCR/CR = 19 vs 22, very good partial response (VGPR) = 48 vs 46, <PR = 34 vs 32
- Best response after R2 (%): sCR/CR = 40 vs 55 (P < 0.001), VGPR = 45 vs 34, <PR = 14 vs 12
- Secondary primary malignancies (SPMs) at 4 years from R2 (pts): 20 vs 27
- 5-year PFS from R2: 41% (median 45 months) vs 48% (median 59 months); all pts = 44% (median 55 months)
- PFS from R2: HR = 0.77; (95% CI 0.63–0.95), P = 0.014)
- PFS benefit from VRD was retained across subgroups:
- Revised ISS stage I: HR = 0.77, (95% CI 0.47–1.27), stage III: HR = 0.76, (95% CI 0.40–1.45)
- Low-risk cytogenetics: HR = 0.79, (95% CI 0.60–1.05), in patients randomized to either VMP: HR = 0.67, (95% CI 0.48-0.94) or HDM: HR = 0.84, (95% CI 0.65–1.09)
- High-risk cytogenetics (del(17p) and/or t(4;14) and/or t(14;16): HR = 1.06, (95% CI 0.70–1.61)
- 5-year OS from R2 = 72% vs 77%
- Adverse events (AEs) from VRD: grade 3/grade 4 (%) = 22/5, neutropenia = 10/2, thrombocytopenia = 9/2; all other AEs were minimal
- Too early to make a conclusion regarding the overall survival (OS)
This interim analysis indicates a beneficial effect on PFS with VRD consolidation followed by lenalidomide maintenance, in younger transplant-eligible patients with MM. The effect was greater in patients that received VMP compared to HDM, and also in patients with standard-risk cytogenetics compared to those with a high-risk profile. VRD consolidation was found to increase CR and sCR. Data for MRD measurements are due to follow.