TY - JOUR
T1 - 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
AU - Wester, Ruth
AU - Van Der Holt, Bronno
AU - Asselbergs, Emelie
AU - Zweegman, Sonja
AU - Kersten, Marie Jose
AU - Vellenga, Edo
AU - Van Marwijk Kooy, Marinus
AU - De Weerdt, Okke
AU - Minnema, Monique
AU - Lonergan, Sarah
AU - Palumbo, Antonio
AU - Lokhorst, Henk
AU - Broijl, Annemiek
AU - Sonneveld, Pieter
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85074306109&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85074306109&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30948492
U2 - https://doi.org/10.3324/haematol.2018.205476
DO - https://doi.org/10.3324/haematol.2018.205476
M3 - Article
C2 - 30948492
SN - 0390-6078
VL - 104
SP - 2265
EP - 2273
JO - Haematologica
JF - Haematologica
IS - 11
ER -