Carfilzomib, Pomalidomide, and Dexamethasone As Second-line Therapy for Lenalidomide-refractory Multiple Myeloma
Pieter Sonneveld,
Sonja Zweegman,
Michele Cavo,
Kazem Nasserinejad,
Annemiek Broijl,
Rosella Troia,
Ludek Pour,
Sandra Croockewit,
Paolo Corradini,
Francesca Patriarca,
Kalung Wu,
Jolanda Droogendijk,
Gerard Bos,
Roman Hajek,
Maria Teresa Petrucci,
Paula Ypma,
Nicholas Zojer,
Monique C. Minnema,
Mario Boccadoro
Affiliations
Pieter Sonneveld
1 Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Sonja Zweegman
2 Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam Cancer Center, The Netherlands
Michele Cavo
3 IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli,” Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università degli Studi, Bologna, Italy
Kazem Nasserinejad
4 Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Annemiek Broijl
1 Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Rosella Troia
5 Hematology, University of Torino, Italy
Ludek Pour
6 Hematology, University Hospital, Brno, Czech Republic
Sandra Croockewit
7 Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands
Paolo Corradini
8 Hematology Division and Hemato-Oncology Department, University of Milan, Fondazione IRCCS Istituto Nazionale dei Tumori, Italy
Francesca Patriarca
9 Hematology and Bone Marrow Transplant Unit, University of Udine, Italy
Kalung Wu
10 Hematology, ZNA Stuivenberg, Antwerpen, Belgium
Jolanda Droogendijk
11 Hematology, Elisabeth Tweesteden Hospital, Tilburg, The Netherlands
Gerard Bos
12 Department of Hematology, University of Maastricht Medical Center, The Netherlands
Roman Hajek
13 Department of Hematology, Ostrava Poruba FNO, Czech Republic
Maria Teresa Petrucci
14 Department of Hematology, La Sapienza, Rome, Italy
Paula Ypma
15 Department of Hematology, Haga Hospital, The Hague, The Netherlands
Nicholas Zojer
16 Department of Hematology, Wilhelminen Hospital, Vienna, Austria
Monique C. Minnema
17 Department of Hematology, University Medical Center Utrecht, Utrecht University, The Netherlands
Mario Boccadoro
18 Department of Molecular Biotechnologies and Health Sciences, Hematology Division, University of Torino, Italy
This phase 2 trial investigated reinduction with carfilzomib, pomalidomide, and dexamethasone (KPd) and continuous pomalidomide/dexamethasone in patients at first progression during lenalidomide maintenance. The second objective was to evaluate high-dose melphalan with autologous stem cell transplantation (HDM/ASCT) at first progression. Patients were eligible who had progressive disease according to International Myeloma Working Group (IMWG) criteria. Treatment consisted of 8 cycles carfilzomib (20/36 mg/m2), pomalidomide (4 mg) and dexamethasone. Patients without prior transplant received HDM/ASCT. Pomalidomide 4 mg w/o dexamethasone was given until progression. One hundred twelve patients were registered of whom 86 (77%) completed 8 cycles of KPd. Thirty-five (85%) eligible patients received HDM/ASCT. The median time to discontinuation of pomalidomide w/o dexamethasone was 17 months. Best response was 37% ≥ complete response, 75% ≥ very good partial response, 92% ≥ partial response, respectively. At a follow-up of 40 months median PFS was 26 and 32 months for patients who received KPd plus HDM/ASCT and 17 months for patients on KPd (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.37-1.00, P = 0.051). PFS was better after longer duration of prior lenalidomide (HR 3.56, 95% CI 1.42-8.96, P = 0.035). Median overall survival (OS) was 67 months. KPd-emerging grade 3 and 4 adverse events included hematologic (41%), cardiovascular (6%), respiratory (3%), infections (17%), and neuropathy (2%). KPd followed by continuous pomalidomide is an effective and safe triple drug regimen in second-line for patients previously exposed to bortezomib and/or refractory to lenalidomide.
