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). During KTd induction therapy, patients received 4 cycles of carfilzomib 20/27 mg/m(2) (n = 50), 20/36 mg/m(2) (n = 20), 20/45 mg/m(2) (n = 21), or 20/56 mg/m(2) (n = 20) on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle; thalidomide 200 mg on days 1 to 28; and dexamethasone 20 mg on days 1, 2, 8, 9, 15, and 16. After autologous stem cell transplantation, patients proceeded to KTd consolidation therapy, where the target doses of carfilzomib were 27 mg/m(2), 36 mg/m(2), 45 mg/m(2), or 56 mg/m(2), 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.

© 2015 by The American Society of Hematology.

Figures

Figure 1

Dosing schedule and treatment schema. Patients received up to 4 cycles (28 days each) of KTd induction therapy before initiating SCH, HDM, and ASCT. Carfilzomib was administered IV over 2 to 10 minutes on days 1, 2, 8, 9, 15, and 16 at a starting dose of 20 mg/m2 for days 1 and 2 of cycle 1 and escalated to a target dose of 27 mg/m2 (cohort 1), 36 mg/m2 (cohort 2), 45 mg/m2 (cohort 3), or 56 mg/m2 (cohort 4, not shown) for days 8, 9, 15, and 16 of cycle 1 and days 1, 2, 8, 9, 15, and 16 of cycles 2 to 4. Thalidomide 200 mg was administered on days 1 to 28, and dexamethasone 20 mg was administered on days 1, 2, 8, 9, 15, and 16. SCH was performed using cyclophosphamide 2 to 4 g/m2 and granulocyte colony-stimulating factor according to institutional protocols. After ASCT, up to 4 cycles (28 days each) of consolidation therapy were initiated. The KTd consolidation regimen was similar to the induction regimen, except that the target doses of carfilzomib and thalidomide were 27 mg/m2 and 50 mg, respectively.

Figure 2

Patient disposition and flow through the study protocol. Cyclo, cyclophosphamide; G-CSF, granulocyte colony-stimulating factor; HD, high-dose; SC, stem cell.

Figure 3

PFS. Kaplan-Meier curve of PFS for all patients (A) and by risk group (B).