LAUSR

This is a phase 2 dose escalation trial of carfilzomib in combination with thalidomide and dexamethasone for induction and consolidation in transplant-eligible patients with newly diagnosed multiple myeloma. The results of 4 dose levels are reported. Induction therapy consisted of 4 cycles of carfilzomib 20/27 mg/m2 (n=50), 20/36 mg/m2 (n=20), 20/45 mg/m2 (n=21) and 20/56 mg/m2 (n=20) on days 1, 2, 8, 9, 15, 16 of a 28-day cycle; thalidomide 200 mg on day 1 through 28 and dexamethasone 40 mg weekly. Induction therapy was followed by high dose melphalan and autologous stem cell transplantation and consolidation therapy with 4 cycles of carfilzomib, thalidomide and dexamethasone in the same schedule except a lower dose of thalidomide (50 mg). Very good partial response rate or better and complete response rate or better after induction therapy were 65% and 18% respectively, increasing to 86% and 63% respectively after consolidation therapy. In all cohorts combined, after a median follow-up of 58.7 months, median progression-free survival was 58 months (95% CI 45-67 months). Median overall survival was 83 months (95% CI 83 months-not reached). Grade 3/4 adverse events consisted mainly of infections, respiratory disorders, skin and vascular disorders in 11%, 8%, 9%, and 9% respectively. Only in 1 patient grade 3 polyneuropathy was reported. Cardiac events were limited, grade 3/4 in 5% of patients. Carfilzomib, thalidomide and dexamethasone as induction and consolidation treatment after high dose melphalan and autologous stem cell transplantation is highly efficacious and safe in transplant-eligible patients with newly diagnosed multiple myeloma. This study was registered at http://www.trialregister.nl as #NTR2422.