Phase 2 study of carfilzomib, thalidomide, and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma.
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.
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands;
Pieter
P
Sonneveld
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands;
Emilie
E
Asselbergs
Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands;
Sonja
S
Zweegman
HOVON Data Center, Erasmus MC Cancer Institute, Clinical Trial Center, Rotterdam, The Netherlands;
Bronno
B
van der Holt
Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands;
Marie Jose
MJ
Kersten
Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands;
Edo
E
Vellenga
Department of Hematology, Isala Clinics, Zwolle, The Netherlands;
Marinus
M
van Marwijk-Kooy
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands;
Annemiek
A
Broyl
Department of Internal Medicine, St. Antonius Hospital, Nieuwegein, The Netherlands;
Okke
O
de Weerdt
Department of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands;
Sarah
S
Lonergan
Myeloma Unit, Division of Hematology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy; and.
Antonio
A
Palumbo
Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
Henk
H
Lokhorst
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009842:Oligopeptides / Q000008:administration & dosage; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage; D055815:Young Adult
D009842:Oligopeptides; D013792:Thalidomide; C524865:carfilzomib; D003907:Dexamethasone