Interim Analysis of Phase II Study of the Bortezomib-Melphalan-Prednisolone Induction Therapy Followed By Lenalidomide-Plus-Dexamethasone Consolidation and Lenalidomide Maintenance in Non-Transplant Eligible Patients with Newly Diagnosed Symptomatic Multiple Myeloma.

Background

In Japan, the phase II study of bortezomib-melphalan-prednisolone (VMP) for NDMM using the same protocol of VISTA trial revealed that there were more treatment discontinuation in this study than in the VISTA study. We planned five cycles of reduced intensity VMP therapy as an induction. And it is reported that lenalidomide plus low dose dexamethasone (Rd) therapy is very effective regimen after VMP therapy. In order to further improve its outcome, patients are treated with six cycles of Rd and maintenance of lenalidomide after VMP induction.

Patients and methods

We included 82 pts with NDMM. Pts were received 5 cycles of VMP followed by 6 cycles of Rd. After Rd, pts received maintenance of lenalidomide. VMP included the IV or SQ administration of weekly bortezomib at 1.3 mg/m² in combination with oral melphalan 6 mg/m² and prednisone 60 mg/m²once daily on days 1 – 4 of a 35-day cycle. Rd treatment consisted of lenalidomide 25 mg daily on days 1-21 plus dexamethasone 40 mg weekly of a 28-day cycle. Lenalidomide maintenance therapy consisted of lenalidomide 10 mg daily on days 1-21 of a 28-day cycle.

Results

In total, 82 pts were recruited in the trial by 27 Japanese centers between 10/2012 and 8/2014. Median age were 73.5 years (range 61 - 84), 37.8% were 75 years of age or older, 45.1% were male, 48.8% had International Staging System (ISS) stage II and 20.7% had ISS stage III. Fifty four patients had IgG-type myeloma (65.8%), 19 had IgA-type (23.2%), and 9 had Bence Jones-type (11%). Of the cases analyzed by FISH (N=80), 16.3% had t(4;14), 10% had del 17p and 41.3% had +1q21. Eight patients (10%) had t(4;14) and +1q21, five patients (6.3%) had del 17p and +1q21 and only one patient (1.3%) had t(4;14), del 17p and +1q21. The best response during VMP therapy (the maximum treatment number was 5 cycles) could be evaluated. After five course of VMP therapy, the rates of partial response (PR) or better were 68% including sCR (5%), CR (6%),VGPR (20%) and PR (37%). The best response rate after VMP+Rd (maximum treatment number of Rd was 6 cycles) was also evaluated. The rates of PR or better were 90% including sCR (6%), CR (16%), VGPR (39%) and PR (29%). The most commonly observed grade 3 or higher adverse events during VMP therapy were anemia (30%), neutropenia (16%), thrombocytopenia (5%) and GI toxicity (6%).

Summary

The induction therapy of reduced intensity VMP was safe and effective. The best response rate after VMP+Rd was very effective. However, we need to evaluate consolidation of Rd and maintenance of lenalidomide after longer follow up.