Phase II study of carfilzomib, thalidomide, and low-dose dexamethasone as induction and consolidation in newly diagnosed, transplant eligible patients with multiple myeloma; the Carthadex trial

This is a phase II dose escalation trial of carfilzomib in combination
with thalidomide and dexamethasone for induction and consolidation in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The results of four dose levels are reported.
Induction therapy consisted of four 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 four 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. Grade 3 polyneuropathy was only reported in
one patient. 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 NDMM. This study was registered as #NTR2422 at
http://www.trialregister.nl