Phase 2 study of carfilzomib, thalidomide, and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma

Abstract

This multicenter phase 2 study of the European Myeloma Network investigated the combination of carfilzomib, thalidomide, and dexamethasone (KTd) as induction/consolidation therapy for transplant-eligible patients with previously untreated multiple myeloma (N = 91). DuringKTdinductiontherapy, patients received 4 cycles of carfilzomib20/27mg/m2 (n = 50), 20/36mg/m2 (n = 20), 20/45 mg/m2 (n = 21),or 20/56mg/m2 (n = 20) on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle; thalidomide 200mg on days 1 to 28; and dexamethasone 20mg on days 1, 2, 8, 9, 15, and 16. After autologous stemcell transplantation, patients proceeded toKTdconsolidation therapy,where the target doses of carfilzomib were 27mg/m2, 36mg/m2, 45 mg/m2, or 56 mg/m2, respectively, and thalidomide 50 mg. Common grade 3/4 adverse events included respiratory (15%), gastrointestinal (12%), and skin disorders (10%); polyneuropathy was infrequent (1%). Complete response rates after induction and consolidation treatment were 25% and 63%, respectively; rates of very good partial response or better after induction and consolidation were 68% and 89%, respectively. At a median follow-up of 23 months, the 36-month progression-free survival rate was 72%. The KTd induction and consolidation regimens were active, safe, and well tolerated. This study was registered at http://www.trialregister.nl as #NTR2422.